It can be very frustrating to be on this protocol and not see the scale go down a pound a day. This is when I really have to be objective about my diet and my actual progress. So for me, I pay attention to everything I eat. Mindful eating I call it. I increase my daily exercise to atleast 30 minutes of aerobics a day and try to drink real water rather than flavor waters, because I really don't know if flavored waters were used in the ORIGINAL protocol back in the 1940s.
It plays on my moods when the scale doesn't move and the fat doesn't leave my body as fast as I think it should or could! I get a little more irritable and sensitive over nothing because of the way I'm feeling internally, which is frustrated! This is all normal on the protocol and sometimes can take 1-2 weeks to pass. It's probably part of the survival mechanism the body has to resist fat loss once I reach around 20 percent body fat. It doesn't mean you are not losing fat in the process so keep looking at yourself in the mirror and pay attention to the places that the fat is leaving and the places where it still exists and be faithful to your goal. This protocol works 100 percent of the time if you will work it 100 percent. So I have to take my own advice and just keep sticking with the program. I have about two weeks to go before I try on those white jeans! I'm hoping they slip on like a nice fitting glove. I'm getting a little bit anxious now though because my body is not cooperating and it might take a little longer than I anticipated.
I will keep you posted! For all of you on the protocol, be strict with yourself and follow a system and you will reach your goals like you never have before with any other weight loss method. I do promise you that.
Call my office in Lombard (630) 627-3700 to set up an appointment or email me at jones.gretchen@gmail.com
hormone replacement therapy, hormone imbalance, women to women, bodylogicmd, hormone replacement after hysterectomy, bioidentical hormones, HRT, women's health, men's health, TS Wiley, The Wiley Protocol
Thursday, May 24, 2012
Monday, May 21, 2012
The Endocrine System - Your Body's Internet
The human endocrine system is sort of like your body's Internet.
It puts out teeny tiny chemical messengers that travel through your bloodstream and cause very big things to happen in your body and with how you feel.
For example, throughout your entire lifetime, the estrogen your endocrine system produces amounts to no more than the weight of a microchip.
But, wow! What an impact it can have on you!
The Way the Endocrine System Works
Your endocrine system is made up of a collection of glands and a few organs that produce hormones. Hormones are small, but powerful little buggers. They regulate and control an extraordinary number of your bodily functions.
Hormones travel by way of your blood through your network of veins and vessels to tell your body what to do and how to feel.
We’re all familiar, in one way or another, with raging hormones in teenagers, pre-menstrual syndrome (PMS) blues and the menopause nightmare. But, it doesn’t have to be that way. Your hormones can work for you instead of against you!
Hormones! How can something so small have such a big impact?
They dramatically affect your health, attitude, growth and development, energy, your sense of security and your feeling of well being.
And, just like a garden needs fertilizer to be healthy and productive, your body’s Internet requires good all-around nutrition and a healthy lifestyle.
You need specific nutrients for your hormones to be balanced and for your glands to function optimally, so you can look and feel your very best. Most important are complete low-fat proteins and high quality oils, especially omega 3 fish oil.
7 Steps for Glandular and Hormonal Health
1. Eat a Healthy Diet. Eating healthy takes diligence and planning. Include more fruits, vegetables, low-fat protein foods and essential oils from fish, whole grains and nuts.
2. Exercise Regularly. Daily exercise is a must for your body to run smoothly and at its best. A daily 30-minute walk or the equivalent is all that's necessary.
3. Manage Stress. Rest, relaxation and letting go of tension and negative emotions are all important. Exercise, meditation and positive-thinking techniques can help.
4. Drink Lots of Water. Water is an essential nutrient. You body prefers at least 8 glasses of pure water a day, without having to distill it out of some other liquid.
5. Live a healthy Lifestyle. Eliminate bad habits such as smoking, eating high glycemic and processed foods and drinking sodas and excess alcohol and coffee.
6. Think Positively. Your mental attitude has a great deal of influence over your health, how your body functions and how you feel. Use your mind to your advantage.
7. Take Good Quality Nutritional Supplements. You can't possibly get everything you need from the food you eat – no matter how good your diet is.
Call my office in Lombard (630) 627-3700 to set up an appointment or email me at jones.gretchen@gmail.com hormone replacement therapy, hormone imbalance, women to women, bodylogicmd, hormone replacement after hysterectomy, bioidentical hormones, HRT, women's health, men's health, TS Wiley, The Wiley Protocol
The human endocrine system is sort of like your body's Internet.
It puts out teeny tiny chemical messengers that travel through your bloodstream and cause very big things to happen in your body and with how you feel.
For example, throughout your entire lifetime, the estrogen your endocrine system produces amounts to no more than the weight of a microchip.
But, wow! What an impact it can have on you!
The Way the Endocrine System Works
Your endocrine system is made up of a collection of glands and a few organs that produce hormones. Hormones are small, but powerful little buggers. They regulate and control an extraordinary number of your bodily functions.
Hormones travel by way of your blood through your network of veins and vessels to tell your body what to do and how to feel.
We’re all familiar, in one way or another, with raging hormones in teenagers, pre-menstrual syndrome (PMS) blues and the menopause nightmare. But, it doesn’t have to be that way. Your hormones can work for you instead of against you!
Hormones! How can something so small have such a big impact?
They dramatically affect your health, attitude, growth and development, energy, your sense of security and your feeling of well being.
And, just like a garden needs fertilizer to be healthy and productive, your body’s Internet requires good all-around nutrition and a healthy lifestyle.
You need specific nutrients for your hormones to be balanced and for your glands to function optimally, so you can look and feel your very best. Most important are complete low-fat proteins and high quality oils, especially omega 3 fish oil.
7 Steps for Glandular and Hormonal Health
1. Eat a Healthy Diet. Eating healthy takes diligence and planning. Include more fruits, vegetables, low-fat protein foods and essential oils from fish, whole grains and nuts.
2. Exercise Regularly. Daily exercise is a must for your body to run smoothly and at its best. A daily 30-minute walk or the equivalent is all that's necessary.
3. Manage Stress. Rest, relaxation and letting go of tension and negative emotions are all important. Exercise, meditation and positive-thinking techniques can help.
4. Drink Lots of Water. Water is an essential nutrient. You body prefers at least 8 glasses of pure water a day, without having to distill it out of some other liquid.
5. Live a healthy Lifestyle. Eliminate bad habits such as smoking, eating high glycemic and processed foods and drinking sodas and excess alcohol and coffee.
6. Think Positively. Your mental attitude has a great deal of influence over your health, how your body functions and how you feel. Use your mind to your advantage.
7. Take Good Quality Nutritional Supplements. You can't possibly get everything you need from the food you eat – no matter how good your diet is.
Call my office in Lombard (630) 627-3700 to set up an appointment or email me at jones.gretchen@gmail.com hormone replacement therapy, hormone imbalance, women to women, bodylogicmd, hormone replacement after hysterectomy, bioidentical hormones, HRT, women's health, men's health, TS Wiley, The Wiley Protocol
DAY 7 OF HCG PROTOCOL
Really!! It's only been a week??? How come it feels like it has been so much longer. I did put myself behind a day or two or three (don't know yet)- because I went to a pool party on Saturday.
I thought I was going to be good and follow my protocol, even brought my own food; apple, chicken, and salad to eat. Everyone knew I was on the protocol and still could not accept that I was fine drinking ice tea and not snacking on all the food that was out.
I knew that if I went to this pool party there was a small chance I would deviate from the protocol, and of course after a couple of hours, I did. This is an annual summer pool party we go to and there is lots of food, drinking, socializing by the hot tub and pool and it lasts all night.
I didn't beat myself up about cheating and started back on track Sunday and planned my meals for today. What I didn't do is get on the scale Sunday or this morning! I didn't want the mental anguish of seeing the scale either the same number or higher. My clothes still are feeling looser so I know intellectually I'm going to reach my goal, but emotionally to see the scale a higher number than what it was the day or two before would be too difficult to handle. I just want to go back to sticking to the protocol and focus on today.
I started listening to Colin Watson's podcasts and that always helps to get me back on track. I choose to focus on what I want, not on what I don't want.
hCG changes lives! It can change yours too!
Call my office in Lombard (630) 627-3700 to set up an appointment or email me at jones.gretchen@gmail.com
hormone replacement therapy, hormone imbalance, women to women, bodylogicmd, hormone replacement after hysterectomy, bioidentical hormones, HRT, women's health, men's health, TS Wiley, The Wiley Protocol
I thought I was going to be good and follow my protocol, even brought my own food; apple, chicken, and salad to eat. Everyone knew I was on the protocol and still could not accept that I was fine drinking ice tea and not snacking on all the food that was out.
I knew that if I went to this pool party there was a small chance I would deviate from the protocol, and of course after a couple of hours, I did. This is an annual summer pool party we go to and there is lots of food, drinking, socializing by the hot tub and pool and it lasts all night.
I didn't beat myself up about cheating and started back on track Sunday and planned my meals for today. What I didn't do is get on the scale Sunday or this morning! I didn't want the mental anguish of seeing the scale either the same number or higher. My clothes still are feeling looser so I know intellectually I'm going to reach my goal, but emotionally to see the scale a higher number than what it was the day or two before would be too difficult to handle. I just want to go back to sticking to the protocol and focus on today.
I started listening to Colin Watson's podcasts and that always helps to get me back on track. I choose to focus on what I want, not on what I don't want.
hCG changes lives! It can change yours too!
Call my office in Lombard (630) 627-3700 to set up an appointment or email me at jones.gretchen@gmail.com
hormone replacement therapy, hormone imbalance, women to women, bodylogicmd, hormone replacement after hysterectomy, bioidentical hormones, HRT, women's health, men's health, TS Wiley, The Wiley Protocol
Friday, May 18, 2012
I wrote this before I weighed in this morning. Yesterday I noticed I had a lot of habits that came to surface that I had to not act on. Urges to randomly snacking throughout the day. What saved me was I was so busy at work that I had no time to rest in between patients. And snacking isn't easy now with braces on my teeth because it is a huge process I have to go through after I eat anything; floss, brush, redo lipstick, etc.
My weight is at my setpoint which is the part where I will stall for a day or two before the pounds drop and mentally that is challenging because when I know I am following the protocol and not losing and I'm exercising, it can be deflating to my efforts. I have to tell myself that I can and will move beyond this temporary stall and that the protocol does work and that fat is dissipating even though the scale doesn't reflect it yet. I tend to sabotage myself at this point in the protocol by eating something a little extra because I'm mad the scale didn't reflect a loss, but who am I punishing - the scale or me?
I have to keep reminding myself that if I keep on track and love myself enough to have the integrity to stay on track, I will reach my goal on time and be able to wear those white jeans by the end of May.
I'm not waking up hungry now. The first couple of days my stomach was feeling really empty and I think to myself how am I not going to eat anything until 10 am. But now, drinking my tea, ice water, or coffee I am fine. I usually have my fruit first and try to stall and not eat lunch until 2:00 or 2:30. Otherwise if I eat at 1:00, I don't really have any time to have a snack or eat until after work which ends sometimes after 6:30-7:00. Yesterday I ate lunch at 1:00 and didn't get a break at work until after 7 so there were thoughts of hunger in that period of time and if I wasn't in the mindset that I was in of sticking with the protocol, I might have snuck in something that was laying around in the lunchroom (and there is never anything low calorie in our lunch room)but I didn't. Instead, I ate an apple when I was done. Drank lots of water. Went to the gym and did a light work out. Came home, grilled some Cod and made a big green salad with salsa and that was dinner.
What is really frustrating about this is that I woke up this morning, got on the scale and it WAS EXACTLY THE SAME WEIGHT AS YESTERDAY MORNING. WHAAAAAATT THE HECK!! Ha Ha, you all know what I'm talking about. That was like a huge slap in the face because of the fact that I was faithful to the protocol. But, this is what I'm talking about. When you reach a "set-point" weight of yours, a weight that your body is comfortable at, it takes some effort to get below it.
So, today, I am sticking with the protocol because I know it works when I follow thru and I will break through this set point. It might stall for a couple of days and I am ready for that stall mentally. I woke up before work and grilled chicken and asparagus for lunch. I am drinking my coffee for breakfast and will have a snack of strawberries around 10 or 11 am today. I'm excited to see the physical response of my body as I go through the changes. It's really motivating too for me to see all my patients who do this protocol and change their lives. I had a family come in yesterday with a total of over 150 lbs of weight loss and tons of inches.
This protocol changes lives. It can change yours too if you want it to.
Call my office in Lombard (630) 627-3700 to set up an appointment or email me at jones.gretchen@gmail.com
hormone replacement therapy, hormone imbalance, women to women, bodylogicmd, hormone replacement after hysterectomy, bioidentical hormones, HRT, women's health, men's health, TS Wiley, The Wiley Protocol
My weight is at my setpoint which is the part where I will stall for a day or two before the pounds drop and mentally that is challenging because when I know I am following the protocol and not losing and I'm exercising, it can be deflating to my efforts. I have to tell myself that I can and will move beyond this temporary stall and that the protocol does work and that fat is dissipating even though the scale doesn't reflect it yet. I tend to sabotage myself at this point in the protocol by eating something a little extra because I'm mad the scale didn't reflect a loss, but who am I punishing - the scale or me?
I have to keep reminding myself that if I keep on track and love myself enough to have the integrity to stay on track, I will reach my goal on time and be able to wear those white jeans by the end of May.
I'm not waking up hungry now. The first couple of days my stomach was feeling really empty and I think to myself how am I not going to eat anything until 10 am. But now, drinking my tea, ice water, or coffee I am fine. I usually have my fruit first and try to stall and not eat lunch until 2:00 or 2:30. Otherwise if I eat at 1:00, I don't really have any time to have a snack or eat until after work which ends sometimes after 6:30-7:00. Yesterday I ate lunch at 1:00 and didn't get a break at work until after 7 so there were thoughts of hunger in that period of time and if I wasn't in the mindset that I was in of sticking with the protocol, I might have snuck in something that was laying around in the lunchroom (and there is never anything low calorie in our lunch room)but I didn't. Instead, I ate an apple when I was done. Drank lots of water. Went to the gym and did a light work out. Came home, grilled some Cod and made a big green salad with salsa and that was dinner.
What is really frustrating about this is that I woke up this morning, got on the scale and it WAS EXACTLY THE SAME WEIGHT AS YESTERDAY MORNING. WHAAAAAATT THE HECK!! Ha Ha, you all know what I'm talking about. That was like a huge slap in the face because of the fact that I was faithful to the protocol. But, this is what I'm talking about. When you reach a "set-point" weight of yours, a weight that your body is comfortable at, it takes some effort to get below it.
So, today, I am sticking with the protocol because I know it works when I follow thru and I will break through this set point. It might stall for a couple of days and I am ready for that stall mentally. I woke up before work and grilled chicken and asparagus for lunch. I am drinking my coffee for breakfast and will have a snack of strawberries around 10 or 11 am today. I'm excited to see the physical response of my body as I go through the changes. It's really motivating too for me to see all my patients who do this protocol and change their lives. I had a family come in yesterday with a total of over 150 lbs of weight loss and tons of inches.
This protocol changes lives. It can change yours too if you want it to.
Call my office in Lombard (630) 627-3700 to set up an appointment or email me at jones.gretchen@gmail.com
hormone replacement therapy, hormone imbalance, women to women, bodylogicmd, hormone replacement after hysterectomy, bioidentical hormones, HRT, women's health, men's health, TS Wiley, The Wiley Protocol
Wednesday, May 16, 2012
Day 4 of hCG Protocol
I'm at my hardest part now of the protocol, and I know it is only Day 4 so don't laugh please. But I am at my weight that I usually can maintain, without dieting. To get below that weight, I really have to fight through some mind games that this protocol brings out.
For those of you that have done this diet you know what I'm talking about. So I came up with some mantras to say to myself when my mind tells me I want to deviate. It's a sort of subliminal discussion I have with myself.
1. I have stuck to my 500 calories a day.
2. I am losing 1-2 lbs a day and I can feel the weight falling off.
3. I am not hungry. There is no need to eat more than 500 calories a day.
4. I am confident this program works.
5. I am following this program perfectly.
6. I have integrity to not sabatoge myself while on this protocol.
7. I am able to stick to my protocol until I reach my goal.
8. This protocol is not difficult and I will reach my goal.
Those are just a few examples that I repeat to myself when I feel like cheating. Cheating just prolongs the goal and I know, I have started and stopped this protocol before with good intentions, but not enough desire to reach a certain goal.
I can't really say I'm ever bored, but I find that I like to eat when I don't want to do something I need to get done. And then I feeeeeel bored. My stomach really isn't growling, and I don't physically need food in my body, but I just feel like eating something that ISN'T on the protocol. It's so funny to fight with myself. It only happens when I do hCG too.
So tomorrow I will post and let you know if the scale stalled or went down and I won't cheat. It's only 5:00 p.m. so I have a long way to go before lights out tonight, but I am going to be true to my word and stick with it. Check out Colin Watson's live broadcast tonight or check out podcasts he has done previously. His broadcasts really help me to stay focused on doing this protocol for me.
Call my office in Lombard (630) 627-3700 to set up an appointment or email me at jones.gretchen@gmail.com
hormone replacement therapy, hormone imbalance, women to women, bodylogicmd, hormone replacement after hysterectomy, bioidentical hormones, HRT, women's health, men's health, TS Wiley, The Wiley Protocol
For those of you that have done this diet you know what I'm talking about. So I came up with some mantras to say to myself when my mind tells me I want to deviate. It's a sort of subliminal discussion I have with myself.
1. I have stuck to my 500 calories a day.
2. I am losing 1-2 lbs a day and I can feel the weight falling off.
3. I am not hungry. There is no need to eat more than 500 calories a day.
4. I am confident this program works.
5. I am following this program perfectly.
6. I have integrity to not sabatoge myself while on this protocol.
7. I am able to stick to my protocol until I reach my goal.
8. This protocol is not difficult and I will reach my goal.
Those are just a few examples that I repeat to myself when I feel like cheating. Cheating just prolongs the goal and I know, I have started and stopped this protocol before with good intentions, but not enough desire to reach a certain goal.
I can't really say I'm ever bored, but I find that I like to eat when I don't want to do something I need to get done. And then I feeeeeel bored. My stomach really isn't growling, and I don't physically need food in my body, but I just feel like eating something that ISN'T on the protocol. It's so funny to fight with myself. It only happens when I do hCG too.
So tomorrow I will post and let you know if the scale stalled or went down and I won't cheat. It's only 5:00 p.m. so I have a long way to go before lights out tonight, but I am going to be true to my word and stick with it. Check out Colin Watson's live broadcast tonight or check out podcasts he has done previously. His broadcasts really help me to stay focused on doing this protocol for me.
Call my office in Lombard (630) 627-3700 to set up an appointment or email me at jones.gretchen@gmail.com
hormone replacement therapy, hormone imbalance, women to women, bodylogicmd, hormone replacement after hysterectomy, bioidentical hormones, HRT, women's health, men's health, TS Wiley, The Wiley Protocol
Tuesday, May 15, 2012
HCG - I'm doing it again!!
Yes, I'm doing hCG again. It isn't easy. I'm on Day 3 of the 500 calorie part. The load day this time was TORTURE for me. Oh my did I do it right! I couldn't sleep the entire night because I was FULL, MISERABLE, HEARTBURN, it was really, really bad.
I worked the entire next day and looked like I had been out partying all night long. Broke my new necklace I had been waiting for in the mail for three months because I was deliriously tired and couldn't figure out how to put it on.
Today, I feel good. I was strict yesterday and didn't cheat at all. Not even with my morning routine of coffee with lots of cream. Down 3.2 pounds after my load day of gaining 4.5 pounds. Lifted weights this morning at the gym before work.
I'm doing this again for two important reasons. The first reason is totally personal. I bought a pair of white jeans from BEBE one or two sizes too small a couple of years ago (and they are literally brand new, never worn) and at the time I was already pretty fit, but because they were the last pair left and I really wanted a pair of white jeans in that particular style, I bought them. Well, my brother just graduated medical school and for his graduation party in June I really, really, really want to be able to wear those white jeans! The second reason is because I promote hCG in my practice and I want to live the walk I talk. I have admittedly started and stopped this protocol in the past, stopping because I couldn't stick to it and gave up within a week or two of starting, gaining a few pounds in the process each time. I went back and evaluated why I would do that to myself over and over again when I was telling my patients to stick to it and be true to yourself and follow the protocol strictly for the best results. I came up with a few revelations. First, I didn't have that much to lose so I wasn't that motivated to be so strict. Second, I succumbed to my emotional eating habits over and over again. I had to identify what those emotions were and why I would want to sabotage myself. It was very eye opening for me to do this. hCG has a way of bringing out all your demons haha.
So, I want to be accountable to all of you who read this blog and come see me in Lombard and help you through the pitfalls of doing this protocol. It works 100% of the time like no other weight loss method out there. When I get into those jeans I will post a facebook picture and you will see why I'm doing the protocol again.
Call my office in Lombard (630) 627-3700 to set up an appointment or email me at jones.gretchen@gmail.com hormone replacement therapy, hormone imbalance, women to women, bodylogicmd, hormone replacement after hysterectomy, bioidentical hormones, HRT, women's health, men's health, TS Wiley, The Wiley Protocol
I worked the entire next day and looked like I had been out partying all night long. Broke my new necklace I had been waiting for in the mail for three months because I was deliriously tired and couldn't figure out how to put it on.
Today, I feel good. I was strict yesterday and didn't cheat at all. Not even with my morning routine of coffee with lots of cream. Down 3.2 pounds after my load day of gaining 4.5 pounds. Lifted weights this morning at the gym before work.
I'm doing this again for two important reasons. The first reason is totally personal. I bought a pair of white jeans from BEBE one or two sizes too small a couple of years ago (and they are literally brand new, never worn) and at the time I was already pretty fit, but because they were the last pair left and I really wanted a pair of white jeans in that particular style, I bought them. Well, my brother just graduated medical school and for his graduation party in June I really, really, really want to be able to wear those white jeans! The second reason is because I promote hCG in my practice and I want to live the walk I talk. I have admittedly started and stopped this protocol in the past, stopping because I couldn't stick to it and gave up within a week or two of starting, gaining a few pounds in the process each time. I went back and evaluated why I would do that to myself over and over again when I was telling my patients to stick to it and be true to yourself and follow the protocol strictly for the best results. I came up with a few revelations. First, I didn't have that much to lose so I wasn't that motivated to be so strict. Second, I succumbed to my emotional eating habits over and over again. I had to identify what those emotions were and why I would want to sabotage myself. It was very eye opening for me to do this. hCG has a way of bringing out all your demons haha.
So, I want to be accountable to all of you who read this blog and come see me in Lombard and help you through the pitfalls of doing this protocol. It works 100% of the time like no other weight loss method out there. When I get into those jeans I will post a facebook picture and you will see why I'm doing the protocol again.
Call my office in Lombard (630) 627-3700 to set up an appointment or email me at jones.gretchen@gmail.com hormone replacement therapy, hormone imbalance, women to women, bodylogicmd, hormone replacement after hysterectomy, bioidentical hormones, HRT, women's health, men's health, TS Wiley, The Wiley Protocol
Thursday, May 10, 2012
Reposted from TS Wiley's newsletter: What Can Your Patients Do To Protect Against Breast Cancer if they are BRCA1 Carriers
What can your Patients do to Protect against Breast Cancer if they are BRCA1 Carriers?
nl_cl_2012_05_06
T.S. Wiley is and always will be a strong proponent of breastfeeding babies into toddler hood, primarily as the single strongest action against preventing breast cancer.
In her book, "Sex, Lies and Menopause", she notes the "collaborative reanalysis of individual data" published in July 2002 in the Lancet, from 47 studies in 30 countries, including 50,302 women with breast cancer and 96,973 women without the disease. "Researchers concluded that if women in developed nations like the United States breast fed nine months longer than the norm, which is three months, breast cancer deaths would be reduced by 25,000 lives. Furthermore, and most importantly, if women breast fed twelve months longer, or fifteen months in total, as is the norm in developing nations, lives saved from breast cancer each year would approach 50,000. Since only about 47,000 of us are expected to die from breast cancer this year, that's all of us who would be saved".
Introduction
Breastfeeding has been inversely related to breast cancer risk in the general population. Clarifying the role of breastfeeding among women with a BRCA1 or BRCA2 mutation may be helpful for risk assessment and for recommendations regarding prevention. We present an updated analysis of breastfeeding and risk of breast cancer using a large matched sample of BRCA mutation carriers.
Methods
We conducted a case-control study of 1,665 pairs of women with a deleterious mutation in either BRCA1 (n = 1,243 pairs) or BRCA2 (n = 422 pairs). Breast cancer cases and unaffected controls were matched on year of birth, mutation status, country of residence and parity. Information about reproductive factors, including breastfeeding for each live birth, was collected from a routinely administered questionnaire. Conditional logistic regression was used to estimate the association between ever having breastfed, as well as total duration of breastfeeding, and the risk of breast cancer.
Results
Among BRCA1 mutation carriers, breastfeeding for at least one year was associated with a 32% reduction in risk (OR = 0.68; 95% CI 0.52 to 0.91; P = 0.008); breastfeeding for two or more years conferred a greater reduction in risk (OR = 0.51; 95% CI 0.35 to 0.74). Among BRCA2 mutation carriers, there was no significant association between breastfeeding for at least one year and breast cancer risk (OR = 0.83; 95% CI 0.53 to 1.31; P = 0.43).
Conclusions
These data extend our previous findings that breastfeeding protects against BRCA1-, but not BRCA2-associated breast cancer. BRCA mutation carriers should be advised of the benefit of breastfeeding in terms of reducing breast cancer risk.
Introduction
In the general population, reproductive factors, including late age at menarche, parity and breastfeeding, have been shown to protect against the development of breast cancer. Various proposed mechanisms include reducing lifetime exposure to ovarian hormones, reducing the cumulative number of ovulatory cycles and differentiation of the breast lobules. We and others have evaluated the impact of reproductive factors in the etiology of BRCA-associated breast cancer, although the results are conflicting and vary by BRCA1 or BRCA2 mutation. With respect to breastfeeding and breast cancer risk in BRCA1 mutation carriers, two previous studies reported no relationship and three studies reported a protective effect. One case-control study of BRCA2 mutation carriers reported no association between breastfeeding and breast cancer risk.
We have previously reported in a study of 965 matched pairs that the total duration of breastfeeding was associated with a significant reduction in breast cancer risk among BRCA1, but not among BRCA2, mutation carriers. The association was particularly strong for breastfeeding for more than one year (OR = 0.55; 95% CI 0.38 to 0.80). No association was seen for BRCA2 mutation carriers (OR = 0.95; 95% CI 0.59 to 1.59). Here we update the analysis of total duration of breastfeeding and risk of breast cancer using a larger sample of BRCA mutation carriers with the addition of 700 matched pairs. Because childbirth and breastfeeding are strongly correlated, we restricted the present analysis to parous women and we matched on parity to eliminate any potential confounding effect of parity.
Methods
Study population
Eligible study subjects were identified at one of 62 participating centers in seven countries. These women were participants in ongoing research protocols at the host institutions. These women sought testing for BRCA1 and BRCA2 mutations because of a personal and/or family history of breast and/or ovarian cancer. All study subjects, (with the exception of some participants from the research study of SLN), received genetic counselling. The institutional review boards of the host institutions approved the study. All subjects provided written informed consent. In most cases, testing was initially offered to women who had been previously diagnosed with breast or ovarian cancer. When a BRCA1 or BRCA2 mutation was identified in a proband or her relative, genetic testing was offered to other at-risk individuals in the family. Mutation detection was performed using a range of techniques, but all nucleotide sequences were confirmed by direct sequencing of DNA. A woman was eligible for the current study when the molecular analysis established that she was a carrier of a deleterious mutation in the BRCA1 or BRCA2 gene.
Data collection
All study subjects completed a baseline questionnaire at the individual center at the time of a clinic appointment or at their home at a later date. The questionnaire requested information on family and personal history of cancer, reproductive and medical histories, including preventive oophorectomy and mastectomy. Detailed information regarding ages at menarche and menopause, cause of menopause, pregnancy, breastfeeding history, and hormone use was also queried. For each live birth, women were asked to recall how long they breastfed each child and to indicate the number of months of breastfeeding. We estimated the total duration of breastfeeding for each woman by summing the months of breastfeeding for each live birth.
Case and control subjects
Information on cancer status was available for a total of 12,116 women who carried a BRCA1 or BRCA2 mutation. Case subjects were women with a diagnosis of invasive breast cancer. Control subjects were women who never had breast cancer and who were also carriers of a mutation in BRCA1 or BRCA2. Potential subjects were excluded if they were nulliparous (n = 2,626) or if information on parity (including year of last birth) was missing (n = 320), if they had been diagnosed with ovarian or other cancer (n = 2,325), if information on breastfeeding was missing (n = 721), if BRCA mutation status was missing (n = 191) or if other pertinent information was missing (n = 54). After exclusions, there was a total of 5,879 eligible women, including 2,784 women with breast cancer (potential case subjects) and 3,095 women without breast cancer (potential control subjects).
A single control subject was selected for each case subject, matched according to mutation in the same gene (BRCA1 or BRCA2), year of birth (within one year), country of residence (Poland, USA, Canada, Israel, Austria, Italy, United Kingdom), and parity (number of births). We only included live births one or more years prior to the breast cancer diagnosis of the case for both the cases and controls. A control was eligible to be matched to a given case if the date of interview or date of prophylactic mastectomy in the matched control occurred at or after the year of breast cancer diagnosis of the case and if the last live birth of the control was at least one calendar year prior to the year of breast cancer diagnosis of the case. In total, 1,665 matched sets were identified. An appropriate match could not be located for 1,119 of the eligible cases because the date of birth of these cases (mean year of birth 1947.99; range 1901 to 1981) was substantially earlier compared to the pool of remaining controls (mean year of birth 1966.57; range 1903 to 1989).
Statistical analysis
A matched case-control analysis was performed to evaluate the association between breastfeeding and the risk of breast cancer. We censored breastfeeding one year prior to the diagnosis of the matched case. The distributions of continuous and categorical variables between cases and controls were compared using the Student's t-test and chi-square test, respectively. Conditional logistic regression was used to estimate the univariate odds ratios (OR) and 95% confidence intervals (CI) for breast cancer associated with breastfeeding (ever/never) and total duration of breastfeeding (months). A multivariate analysis was carried out to control for potential confounders. All analyses were performed using the SAS statistical package, version 9.1.3 (SAS Institute, Cary, NC, USA). All P-values were based on two-sided tests and were considered statistically significant if P ≤ 0.05.
Results
Case and control subjects were similar with respect to year of birth, oral contraceptive use, age at last birth, smoking status and body mass index (BMI) at age 30 (Table 1). Cases with a BRCA1 mutation had a significantly earlier age at menarche than controls (13.09 years vs. 13.27 years; P = 0.003) and were less likely to have consumed alcohol (61% vs. 67%; P = 0.002). Although not significant, age at first birth (24.8 vs. 25.1; P = 0.08) and age at last birth (29.0 vs. 29.3; P = 0.06) were, on average, earlier in BRCA1 mutation carriers compared with controls. Hormone replacement therapy (HRT) use was significantly lower in both BRCA1 and BRCA2 cases versus controls (5% vs. 12%; P < 0.0001 and 10.7% vs. 16.5%; P = 0.02, respectively). Age at menarche, age at first birth, age at last birth, mean duration of breastfeeding and alcohol consumption did not differ between cases and controls with a BRCA2 mutation.
Table 1. Baseline characteristics of breast cancer cases and controls with BRCA1 and BRCA2 mutations.
The mean duration of breastfeeding was shorter among the cases than the controls with a BRCA1 mutation (8.8 months vs. 10.4 months; P = 0.0009). There was a significant reduction in breast cancer risk with breastfeeding among women with a BRCA1 but not a BRCA2 mutation (Table 2). On average, BRCA1 cases breastfed for 1.6 fewer months than controls (8.8 vs. 10.4 months P = 0.0009). There was only a 0.5-month difference between cases and controls with a BRCA2 mutation (10.2 vs. 9.7 months P = 0.56). Among BRCA1 mutation carriers, breastfeeding for at least one year was associated with a 32% reduction in risk (OR = 0.68; 95% CI 0.52 to 0.91; P = 0.008); breastfeeding for two or more years conferred an even stronger reduction in risk (OR = 0.51; 95% CI 0.35 to 0.74; P = 0.0003). Each year of breastfeeding conferred a 19% reduction in risk. The effect of breastfeeding was present for women diagnosed at all ages. The reduction in risk associated with breastfeeding for one or more years compared with never breastfeeding was 44% for women with an age at breast cancer diagnosis of ≤ 39 (OR = 0.56; 95% CI 0.33 to 0.96), 54% for those with an age at diagnosis of 40 to 49 (OR = 0.46; 95% CI 0.26 to .81) and 69% for those with an age at diagnosis of ≥ 50 (OR = 0.31; 95% CI 0.07 to 1.30).
Table 2. Relationship between duration of breastfeeding and risk of breast cancer among BRCA1 and BRCA2 mutation carriers.
Among BRCA2 mutation carriers, there was no significant association between breastfeeding for at least one year and breast cancer risk (OR = 0.83; 95% CI 0.53 to 1.31; P = 0.43). There was no relationship following stratification by age at diagnosis. The risk estimates associated with breastfeeding for one or more years compared with never breastfeeding by age at diagnoses ≤ 39, 40 to 49 and ≥ 50 were 0.98 (95% CI 0.37 to 2.62), 1.41 (95% CI 0.59 to 3.43) and 0.91 (95% CI 0.24 to 3.43), respectively.
Discussion
The goal of the current study was to evaluate the relationship between breastfeeding and breast cancer risk among women with a BRCA1 or BRCA2 mutation. Because of the strong relationship between parity and breastfeeding, we limited our analysis to parous women and we matched cases and controls on parity. Here we report that ever having breastfed and the total duration of breastfeeding conferred substantial reductions in breast cancer risk among BRCA1, but not BRCA2 mutation carriers. Breastfeeding for one or more years conferred a significant 32% reduction in risk in BRCA1 mutation carriers. These findings are in agreement with our earlier publication, which was based on a subset of these women. In the present study, we expand our study sample from 995 to 1,665 matched pairs and we have matched on parity. The current study provides the most up-to-date evaluation of this association and should be helpful for genetic counsellors. The current study pertains to women who choose not to have a bilateral mastectomy; among women who have had preventive surgery, the risk of breast cancer is sufficiently low that they are not impacted adversely by the inability to breastfeed.
Other groups that have evaluated the relationship between breastfeeding and breast cancer risk among BRCA mutation carriers reported no relationship between breastfeeding and risk, although these studies were limited by small sample sizes and the merging of women who were carriers of a BRCA1 or BRCA2 mutation. These findings extend our previous report that breastfeeding for more than one year reduces risk among BRCA1, but not among BRCA2 mutation carriers.
In a collaborative re-analysis of data from 47 independent epidemiologic studies conducted among women in the general population, the authors reported a 4.3% reduction in breast cancer risk for every 12 months of breastfeeding (95% CI 2.9 to 5.8; P < 0.0001). The effect of breastfeeding among BRCA1 mutation carriers reported here is much greater than that reported in the general population (19% vs. 4.3% reduction in risk per year of breastfeeding). In BRCA mutation carriers specifically, it does not appear that parity per se influences the risk of breast cancer independently of breastfeeding. The majority of BRCA1-related tumors are basal-like breast cancers characterized by ER, PR and HER2 negativity while BRCA2-tumors resemble sporadic cases. Other groups have shown that parity is a risk factor, while breastfeeding protects against the development of basal-like or ER-negative/PR-negative breast cancers in the general population. Likewise, differences in the pathologic features of BRCA1 and BRCA2 tumors may also reflect etiologically distinct tumors and possibly differences in risk factor associations.
Several mechanisms have been proposed to explain the biologic basis for the inverse relationship between breastfeeding and breast cancer risk. These include: 1) hormonal changes, particularly a reduction in endogenous estrogen and progesterone levels and/or increased prolactin levels; 2) excretion of estrogens and carcinogens from the breast ducts; 3) breast tissue differentiation; and 4) a delay in the establishment of regular ovulation and, subsequently, the cumulative number of ovulatory cycles. We have recently shown that the number of lifetime ovulatory cycles does not influence breast cancer risk in women with BRCA1 or BRCA2 mutations (JK, JL, HTL, C K-S, SN, RD, WDF, PG, NT, PA, LS, Beth Karlan, AE, CE, Jeffrey Weitzel, DMG, JB, Dana Zakalik, CS, Taya Fallen, OG, TH, PS, SAN, Oophorectomy after Menopause and the Risk of Breast Cancer in BRCA1 and BRCA2 Mutation Carriers, submitted). Our data presented in this manuscript support the first three hypotheses and are reinforced by the long lasting effect of breastfeeding among BRCA1 mutation carriers. Breastfeeding for at least one year significantly reduced the risk of breast cancer diagnosed under the age of 50. Although the association did not achieve statistical significance (likely due to small numbers), this protective effect was also apparent for those diagnosed ≥ 50 and was indicative of a long-term reduction in risk with breastfeeding.
Experimental evidence supports an important role of the BRCA1 protein in mammary cell differentiation and proliferation. Rajan and colleagues have shown that BRCA1 and BRCA2 mRNA expression is high in proliferating cells in mice during periods of rapid proliferation and differentiation, such as embryogenesis, puberty and pregnancy, but is low during lactation. In addition, the BRCA proteins interact with STAT5a, a mammary gland transcription factor that is stimulated by prolactin at the end of pregnancy, and which is involved in the growth and terminal differentiation of breast epithelial cells. Thus, among women with a mutation and one functional allele, one would expect that breast cell differentiation from breastfeeding might be compromised.
In vivo studies have shown that a conditional mutation in Brca1 in mouse mammary epithelial cells results in defective development of mammary tissue during pregnancy and lactation. Further, Russo et al. have reported that the developmental pattern of breast tissue from parous women with a family history of breast cancer or BRCA1 mutation was comparable to that from nulliparous women with no family history (that is, did not differentiate with parity). Collectively, the evidence supports an important role of the BRCA proteins in breast tissue differentiation during pregnancy and/or lactation.
Based on our findings to date, it appears that cumulative sex hormone exposure, particularly estrogen, is likely involved in the development of breast cancer in BRCA1 mutation carriers. Late age at menarche, breastfeeding and bilateral salpingo-oophorectomy are protective; while the role of parity is less clear. Recent studies have identified an important role for progesterone in regulating the number of stem cells in normal human and mouse mammary glands. The terminal differentiation of mammary stem cells during the process of breastfeeding may be protective since this process can deplete the pool of potentially deleterious stem cells or by reducing the number of stem cells at risk of mutation. If confirmed, agents that can mimic the terminal differentiation process, or otherwise reduce the size of the stem cell population, may be effective in reducing breast cancer risk. Notably, it has been reported that heterozygosity of BRCA1 may result in abnormal self-renewal of breast cancer stem cells. Specifically, failure of terminal differentiation after pregnancy in BRCA1 mutation carriers resulted in an increased risk of breast cancer.
Strengths of the current study include the large number of known BRCA mutation carriers and the ability to conduct a matched analysis to ensure that the case and control subjects were similar. The sample size range in four prior studies was 94 to 1,601 BRCA carriers . To determine the effect of breastfeeding on cancer risk independent of the effects of parity, we limited our analysis to parous women and matched for parity. We controlled for other known or suspected risk factors for breast cancer in our multivariate models, thus decreasing the influence of confounding although our adjusted and unadjusted results did not differ substantially.
The main limitation of our study was the use of self-reported breastfeeding which may have led to measurement error; however, an earlier validation study by Kark et al. reported high concordance between breastfeeding derived from clinic records compared with an interview conducted 20 to 22 years later (Spearman P = 0.86). A role of recall bias is unlikely given that there is no reason for women to suspect a role of breastfeeding in the etiology of their disease. In addition, we were not able to differentiate between women who exclusively breastfed versus those who also supplemented with bottle feeding. Despite this, with 1,665 matched pairs, this is the largest study to date addressing the role of breastfeeding in the etiology of BRCA-associated breast cancer development.
Conclusions
In summary, these findings corroborate a protective role of breastfeeding on breast cancer risk for BRCA1. The lack of an association for BRCA2 mutation carriers suggests that the biological pathway for carcinogenesis is different for the two genes. Women with a BRCA mutation should be advised of the benefit of breastfeeding in terms of reducing breast cancer risk.
T.S. Wiley concludes, “This new study just reinforces these beliefs and gives us further information to aid BRCA1 carriers.”
Steven A Narod and TS Wiley
Call my office in Lombard (630) 627-3700 to set up an appointment or email me at jones.gretchen@gmail.com
nl_cl_2012_05_06
T.S. Wiley is and always will be a strong proponent of breastfeeding babies into toddler hood, primarily as the single strongest action against preventing breast cancer.
In her book, "Sex, Lies and Menopause", she notes the "collaborative reanalysis of individual data" published in July 2002 in the Lancet, from 47 studies in 30 countries, including 50,302 women with breast cancer and 96,973 women without the disease. "Researchers concluded that if women in developed nations like the United States breast fed nine months longer than the norm, which is three months, breast cancer deaths would be reduced by 25,000 lives. Furthermore, and most importantly, if women breast fed twelve months longer, or fifteen months in total, as is the norm in developing nations, lives saved from breast cancer each year would approach 50,000. Since only about 47,000 of us are expected to die from breast cancer this year, that's all of us who would be saved".
Introduction
Breastfeeding has been inversely related to breast cancer risk in the general population. Clarifying the role of breastfeeding among women with a BRCA1 or BRCA2 mutation may be helpful for risk assessment and for recommendations regarding prevention. We present an updated analysis of breastfeeding and risk of breast cancer using a large matched sample of BRCA mutation carriers.
Methods
We conducted a case-control study of 1,665 pairs of women with a deleterious mutation in either BRCA1 (n = 1,243 pairs) or BRCA2 (n = 422 pairs). Breast cancer cases and unaffected controls were matched on year of birth, mutation status, country of residence and parity. Information about reproductive factors, including breastfeeding for each live birth, was collected from a routinely administered questionnaire. Conditional logistic regression was used to estimate the association between ever having breastfed, as well as total duration of breastfeeding, and the risk of breast cancer.
Results
Among BRCA1 mutation carriers, breastfeeding for at least one year was associated with a 32% reduction in risk (OR = 0.68; 95% CI 0.52 to 0.91; P = 0.008); breastfeeding for two or more years conferred a greater reduction in risk (OR = 0.51; 95% CI 0.35 to 0.74). Among BRCA2 mutation carriers, there was no significant association between breastfeeding for at least one year and breast cancer risk (OR = 0.83; 95% CI 0.53 to 1.31; P = 0.43).
Conclusions
These data extend our previous findings that breastfeeding protects against BRCA1-, but not BRCA2-associated breast cancer. BRCA mutation carriers should be advised of the benefit of breastfeeding in terms of reducing breast cancer risk.
Introduction
In the general population, reproductive factors, including late age at menarche, parity and breastfeeding, have been shown to protect against the development of breast cancer. Various proposed mechanisms include reducing lifetime exposure to ovarian hormones, reducing the cumulative number of ovulatory cycles and differentiation of the breast lobules. We and others have evaluated the impact of reproductive factors in the etiology of BRCA-associated breast cancer, although the results are conflicting and vary by BRCA1 or BRCA2 mutation. With respect to breastfeeding and breast cancer risk in BRCA1 mutation carriers, two previous studies reported no relationship and three studies reported a protective effect. One case-control study of BRCA2 mutation carriers reported no association between breastfeeding and breast cancer risk.
We have previously reported in a study of 965 matched pairs that the total duration of breastfeeding was associated with a significant reduction in breast cancer risk among BRCA1, but not among BRCA2, mutation carriers. The association was particularly strong for breastfeeding for more than one year (OR = 0.55; 95% CI 0.38 to 0.80). No association was seen for BRCA2 mutation carriers (OR = 0.95; 95% CI 0.59 to 1.59). Here we update the analysis of total duration of breastfeeding and risk of breast cancer using a larger sample of BRCA mutation carriers with the addition of 700 matched pairs. Because childbirth and breastfeeding are strongly correlated, we restricted the present analysis to parous women and we matched on parity to eliminate any potential confounding effect of parity.
Methods
Study population
Eligible study subjects were identified at one of 62 participating centers in seven countries. These women were participants in ongoing research protocols at the host institutions. These women sought testing for BRCA1 and BRCA2 mutations because of a personal and/or family history of breast and/or ovarian cancer. All study subjects, (with the exception of some participants from the research study of SLN), received genetic counselling. The institutional review boards of the host institutions approved the study. All subjects provided written informed consent. In most cases, testing was initially offered to women who had been previously diagnosed with breast or ovarian cancer. When a BRCA1 or BRCA2 mutation was identified in a proband or her relative, genetic testing was offered to other at-risk individuals in the family. Mutation detection was performed using a range of techniques, but all nucleotide sequences were confirmed by direct sequencing of DNA. A woman was eligible for the current study when the molecular analysis established that she was a carrier of a deleterious mutation in the BRCA1 or BRCA2 gene.
Data collection
All study subjects completed a baseline questionnaire at the individual center at the time of a clinic appointment or at their home at a later date. The questionnaire requested information on family and personal history of cancer, reproductive and medical histories, including preventive oophorectomy and mastectomy. Detailed information regarding ages at menarche and menopause, cause of menopause, pregnancy, breastfeeding history, and hormone use was also queried. For each live birth, women were asked to recall how long they breastfed each child and to indicate the number of months of breastfeeding. We estimated the total duration of breastfeeding for each woman by summing the months of breastfeeding for each live birth.
Case and control subjects
Information on cancer status was available for a total of 12,116 women who carried a BRCA1 or BRCA2 mutation. Case subjects were women with a diagnosis of invasive breast cancer. Control subjects were women who never had breast cancer and who were also carriers of a mutation in BRCA1 or BRCA2. Potential subjects were excluded if they were nulliparous (n = 2,626) or if information on parity (including year of last birth) was missing (n = 320), if they had been diagnosed with ovarian or other cancer (n = 2,325), if information on breastfeeding was missing (n = 721), if BRCA mutation status was missing (n = 191) or if other pertinent information was missing (n = 54). After exclusions, there was a total of 5,879 eligible women, including 2,784 women with breast cancer (potential case subjects) and 3,095 women without breast cancer (potential control subjects).
A single control subject was selected for each case subject, matched according to mutation in the same gene (BRCA1 or BRCA2), year of birth (within one year), country of residence (Poland, USA, Canada, Israel, Austria, Italy, United Kingdom), and parity (number of births). We only included live births one or more years prior to the breast cancer diagnosis of the case for both the cases and controls. A control was eligible to be matched to a given case if the date of interview or date of prophylactic mastectomy in the matched control occurred at or after the year of breast cancer diagnosis of the case and if the last live birth of the control was at least one calendar year prior to the year of breast cancer diagnosis of the case. In total, 1,665 matched sets were identified. An appropriate match could not be located for 1,119 of the eligible cases because the date of birth of these cases (mean year of birth 1947.99; range 1901 to 1981) was substantially earlier compared to the pool of remaining controls (mean year of birth 1966.57; range 1903 to 1989).
Statistical analysis
A matched case-control analysis was performed to evaluate the association between breastfeeding and the risk of breast cancer. We censored breastfeeding one year prior to the diagnosis of the matched case. The distributions of continuous and categorical variables between cases and controls were compared using the Student's t-test and chi-square test, respectively. Conditional logistic regression was used to estimate the univariate odds ratios (OR) and 95% confidence intervals (CI) for breast cancer associated with breastfeeding (ever/never) and total duration of breastfeeding (months). A multivariate analysis was carried out to control for potential confounders. All analyses were performed using the SAS statistical package, version 9.1.3 (SAS Institute, Cary, NC, USA). All P-values were based on two-sided tests and were considered statistically significant if P ≤ 0.05.
Results
Case and control subjects were similar with respect to year of birth, oral contraceptive use, age at last birth, smoking status and body mass index (BMI) at age 30 (Table 1). Cases with a BRCA1 mutation had a significantly earlier age at menarche than controls (13.09 years vs. 13.27 years; P = 0.003) and were less likely to have consumed alcohol (61% vs. 67%; P = 0.002). Although not significant, age at first birth (24.8 vs. 25.1; P = 0.08) and age at last birth (29.0 vs. 29.3; P = 0.06) were, on average, earlier in BRCA1 mutation carriers compared with controls. Hormone replacement therapy (HRT) use was significantly lower in both BRCA1 and BRCA2 cases versus controls (5% vs. 12%; P < 0.0001 and 10.7% vs. 16.5%; P = 0.02, respectively). Age at menarche, age at first birth, age at last birth, mean duration of breastfeeding and alcohol consumption did not differ between cases and controls with a BRCA2 mutation.
Table 1. Baseline characteristics of breast cancer cases and controls with BRCA1 and BRCA2 mutations.
The mean duration of breastfeeding was shorter among the cases than the controls with a BRCA1 mutation (8.8 months vs. 10.4 months; P = 0.0009). There was a significant reduction in breast cancer risk with breastfeeding among women with a BRCA1 but not a BRCA2 mutation (Table 2). On average, BRCA1 cases breastfed for 1.6 fewer months than controls (8.8 vs. 10.4 months P = 0.0009). There was only a 0.5-month difference between cases and controls with a BRCA2 mutation (10.2 vs. 9.7 months P = 0.56). Among BRCA1 mutation carriers, breastfeeding for at least one year was associated with a 32% reduction in risk (OR = 0.68; 95% CI 0.52 to 0.91; P = 0.008); breastfeeding for two or more years conferred an even stronger reduction in risk (OR = 0.51; 95% CI 0.35 to 0.74; P = 0.0003). Each year of breastfeeding conferred a 19% reduction in risk. The effect of breastfeeding was present for women diagnosed at all ages. The reduction in risk associated with breastfeeding for one or more years compared with never breastfeeding was 44% for women with an age at breast cancer diagnosis of ≤ 39 (OR = 0.56; 95% CI 0.33 to 0.96), 54% for those with an age at diagnosis of 40 to 49 (OR = 0.46; 95% CI 0.26 to .81) and 69% for those with an age at diagnosis of ≥ 50 (OR = 0.31; 95% CI 0.07 to 1.30).
Table 2. Relationship between duration of breastfeeding and risk of breast cancer among BRCA1 and BRCA2 mutation carriers.
Among BRCA2 mutation carriers, there was no significant association between breastfeeding for at least one year and breast cancer risk (OR = 0.83; 95% CI 0.53 to 1.31; P = 0.43). There was no relationship following stratification by age at diagnosis. The risk estimates associated with breastfeeding for one or more years compared with never breastfeeding by age at diagnoses ≤ 39, 40 to 49 and ≥ 50 were 0.98 (95% CI 0.37 to 2.62), 1.41 (95% CI 0.59 to 3.43) and 0.91 (95% CI 0.24 to 3.43), respectively.
Discussion
The goal of the current study was to evaluate the relationship between breastfeeding and breast cancer risk among women with a BRCA1 or BRCA2 mutation. Because of the strong relationship between parity and breastfeeding, we limited our analysis to parous women and we matched cases and controls on parity. Here we report that ever having breastfed and the total duration of breastfeeding conferred substantial reductions in breast cancer risk among BRCA1, but not BRCA2 mutation carriers. Breastfeeding for one or more years conferred a significant 32% reduction in risk in BRCA1 mutation carriers. These findings are in agreement with our earlier publication, which was based on a subset of these women. In the present study, we expand our study sample from 995 to 1,665 matched pairs and we have matched on parity. The current study provides the most up-to-date evaluation of this association and should be helpful for genetic counsellors. The current study pertains to women who choose not to have a bilateral mastectomy; among women who have had preventive surgery, the risk of breast cancer is sufficiently low that they are not impacted adversely by the inability to breastfeed.
Other groups that have evaluated the relationship between breastfeeding and breast cancer risk among BRCA mutation carriers reported no relationship between breastfeeding and risk, although these studies were limited by small sample sizes and the merging of women who were carriers of a BRCA1 or BRCA2 mutation. These findings extend our previous report that breastfeeding for more than one year reduces risk among BRCA1, but not among BRCA2 mutation carriers.
In a collaborative re-analysis of data from 47 independent epidemiologic studies conducted among women in the general population, the authors reported a 4.3% reduction in breast cancer risk for every 12 months of breastfeeding (95% CI 2.9 to 5.8; P < 0.0001). The effect of breastfeeding among BRCA1 mutation carriers reported here is much greater than that reported in the general population (19% vs. 4.3% reduction in risk per year of breastfeeding). In BRCA mutation carriers specifically, it does not appear that parity per se influences the risk of breast cancer independently of breastfeeding. The majority of BRCA1-related tumors are basal-like breast cancers characterized by ER, PR and HER2 negativity while BRCA2-tumors resemble sporadic cases. Other groups have shown that parity is a risk factor, while breastfeeding protects against the development of basal-like or ER-negative/PR-negative breast cancers in the general population. Likewise, differences in the pathologic features of BRCA1 and BRCA2 tumors may also reflect etiologically distinct tumors and possibly differences in risk factor associations.
Several mechanisms have been proposed to explain the biologic basis for the inverse relationship between breastfeeding and breast cancer risk. These include: 1) hormonal changes, particularly a reduction in endogenous estrogen and progesterone levels and/or increased prolactin levels; 2) excretion of estrogens and carcinogens from the breast ducts; 3) breast tissue differentiation; and 4) a delay in the establishment of regular ovulation and, subsequently, the cumulative number of ovulatory cycles. We have recently shown that the number of lifetime ovulatory cycles does not influence breast cancer risk in women with BRCA1 or BRCA2 mutations (JK, JL, HTL, C K-S, SN, RD, WDF, PG, NT, PA, LS, Beth Karlan, AE, CE, Jeffrey Weitzel, DMG, JB, Dana Zakalik, CS, Taya Fallen, OG, TH, PS, SAN, Oophorectomy after Menopause and the Risk of Breast Cancer in BRCA1 and BRCA2 Mutation Carriers, submitted). Our data presented in this manuscript support the first three hypotheses and are reinforced by the long lasting effect of breastfeeding among BRCA1 mutation carriers. Breastfeeding for at least one year significantly reduced the risk of breast cancer diagnosed under the age of 50. Although the association did not achieve statistical significance (likely due to small numbers), this protective effect was also apparent for those diagnosed ≥ 50 and was indicative of a long-term reduction in risk with breastfeeding.
Experimental evidence supports an important role of the BRCA1 protein in mammary cell differentiation and proliferation. Rajan and colleagues have shown that BRCA1 and BRCA2 mRNA expression is high in proliferating cells in mice during periods of rapid proliferation and differentiation, such as embryogenesis, puberty and pregnancy, but is low during lactation. In addition, the BRCA proteins interact with STAT5a, a mammary gland transcription factor that is stimulated by prolactin at the end of pregnancy, and which is involved in the growth and terminal differentiation of breast epithelial cells. Thus, among women with a mutation and one functional allele, one would expect that breast cell differentiation from breastfeeding might be compromised.
In vivo studies have shown that a conditional mutation in Brca1 in mouse mammary epithelial cells results in defective development of mammary tissue during pregnancy and lactation. Further, Russo et al. have reported that the developmental pattern of breast tissue from parous women with a family history of breast cancer or BRCA1 mutation was comparable to that from nulliparous women with no family history (that is, did not differentiate with parity). Collectively, the evidence supports an important role of the BRCA proteins in breast tissue differentiation during pregnancy and/or lactation.
Based on our findings to date, it appears that cumulative sex hormone exposure, particularly estrogen, is likely involved in the development of breast cancer in BRCA1 mutation carriers. Late age at menarche, breastfeeding and bilateral salpingo-oophorectomy are protective; while the role of parity is less clear. Recent studies have identified an important role for progesterone in regulating the number of stem cells in normal human and mouse mammary glands. The terminal differentiation of mammary stem cells during the process of breastfeeding may be protective since this process can deplete the pool of potentially deleterious stem cells or by reducing the number of stem cells at risk of mutation. If confirmed, agents that can mimic the terminal differentiation process, or otherwise reduce the size of the stem cell population, may be effective in reducing breast cancer risk. Notably, it has been reported that heterozygosity of BRCA1 may result in abnormal self-renewal of breast cancer stem cells. Specifically, failure of terminal differentiation after pregnancy in BRCA1 mutation carriers resulted in an increased risk of breast cancer.
Strengths of the current study include the large number of known BRCA mutation carriers and the ability to conduct a matched analysis to ensure that the case and control subjects were similar. The sample size range in four prior studies was 94 to 1,601 BRCA carriers . To determine the effect of breastfeeding on cancer risk independent of the effects of parity, we limited our analysis to parous women and matched for parity. We controlled for other known or suspected risk factors for breast cancer in our multivariate models, thus decreasing the influence of confounding although our adjusted and unadjusted results did not differ substantially.
The main limitation of our study was the use of self-reported breastfeeding which may have led to measurement error; however, an earlier validation study by Kark et al. reported high concordance between breastfeeding derived from clinic records compared with an interview conducted 20 to 22 years later (Spearman P = 0.86). A role of recall bias is unlikely given that there is no reason for women to suspect a role of breastfeeding in the etiology of their disease. In addition, we were not able to differentiate between women who exclusively breastfed versus those who also supplemented with bottle feeding. Despite this, with 1,665 matched pairs, this is the largest study to date addressing the role of breastfeeding in the etiology of BRCA-associated breast cancer development.
Conclusions
In summary, these findings corroborate a protective role of breastfeeding on breast cancer risk for BRCA1. The lack of an association for BRCA2 mutation carriers suggests that the biological pathway for carcinogenesis is different for the two genes. Women with a BRCA mutation should be advised of the benefit of breastfeeding in terms of reducing breast cancer risk.
T.S. Wiley concludes, “This new study just reinforces these beliefs and gives us further information to aid BRCA1 carriers.”
Steven A Narod and TS Wiley
Call my office in Lombard (630) 627-3700 to set up an appointment or email me at jones.gretchen@gmail.com
LOW ESTROGEN? WHAT DOES THAT MEAN??
Hypoestrogen, What is that?
Women of all ages can have hypoestrogen. Hypoestrogen is when levels of cycling estrogen falls below the normal range of 150 pg/ml to 550 pg/ml. The symptoms are felt by women in many ways. And every woman knows when “the change” happens. Some women even know when slight changes begin to occur. Even the women who are lucky enough to never experience a hot flash often have probably experienced one of the following other hypoestrogen symptoms: heart palpitations, insomnia, mood swings, joint aches, headaches, fatigue, low libido, vaginal dryness, bloating, skin dryness, brain fog….just to name a few.
When just a few symptoms began to occur with me at age 42, I was NOT thinking it was from hypoestrogen. I knew that to be “menopause” and I was still cycling every 28 days having a 3-4 day period and just had two babies 15 months apart. When my doctor told me I should start on beta blockers to control my anxiety feelings and onset of heart palpitations, I decided to dig really deep and figure out what was causing the changes in my body to occur. I knew these changes came out of no where started to occur shortly after my last pregnancy at age 41. At that time my estrogen level was 48 pg/ml. I didn’t know much about fractionating the estradiol out of the estrogen total at that time. I didn’t know what the significance was about timing the cycling and checking blood. I didn’t know that fluctuations in estrogen can be pretty significant just days apart in a cycle. I also didn’t realize that if estrogen wasn’t peaking and I wasn’t ovulating I was not getting any progesterone and therefore had cycles with unopposed estrogen.
I’ve been treating women who have hypoestrogen levels and have seen the dramatic changes that occur when estrogen and progesterone are replaced in a cyclic dosing schedule and reach their individual therapeutic range in the blood serum. Like I said earlier, estrogen peaks around 350-550 pg/ml and is around 100-150 pg/ml on baseline days. Progesterone peaks around 10-15 ng/ml and is around 2-5 ng/ml on baseline days. Hormones that are too low cause symptoms that women feel and experience. They are real symptoms.
How long would you replace your thyroid if you were hypothyroid? I believe you would say forever. Well, I say that is how long we should replace our estrogen and progesterone if we have hypoestrogen. The results are amazing. It’s easier to replace hormones when receptors are still present and active. But, it is never too late. I have patients who are doing amazingly well that are in their late 70’s. I also have patients as young as 19 whose symptoms are resolved dramatically using bioidentical hormones in cyclic dosing and the results cannot even compare to that of traditional care, which is oral birth control pills (synthetic estrogen and synthetic progestins) given in static doses using low amounts of hormones. I know many women who cannot stand how they feel on the pill. Maybe some women don’t even realize that it is the pill causing some of the symptoms they experience.
Women can change the standard of care. My goal is to educate women and then we have a choice what we want to do with that information. We cycle. Let’s keep on cycling.
Hypoestrogen, What is that?
Lombard (630) 627-3700 to set up an appointment or email me at jones.gretchen@gmail.com
Women of all ages can have hypoestrogen. Hypoestrogen is when levels of cycling estrogen falls below the normal range of 150 pg/ml to 550 pg/ml. The symptoms are felt by women in many ways. And every woman knows when “the change” happens. Some women even know when slight changes begin to occur. Even the women who are lucky enough to never experience a hot flash often have probably experienced one of the following other hypoestrogen symptoms: heart palpitations, insomnia, mood swings, joint aches, headaches, fatigue, low libido, vaginal dryness, bloating, skin dryness, brain fog….just to name a few.
When just a few symptoms began to occur with me at age 42, I was NOT thinking it was from hypoestrogen. I knew that to be “menopause” and I was still cycling every 28 days having a 3-4 day period and just had two babies 15 months apart. When my doctor told me I should start on beta blockers to control my anxiety feelings and onset of heart palpitations, I decided to dig really deep and figure out what was causing the changes in my body to occur. I knew these changes came out of no where started to occur shortly after my last pregnancy at age 41. At that time my estrogen level was 48 pg/ml. I didn’t know much about fractionating the estradiol out of the estrogen total at that time. I didn’t know what the significance was about timing the cycling and checking blood. I didn’t know that fluctuations in estrogen can be pretty significant just days apart in a cycle. I also didn’t realize that if estrogen wasn’t peaking and I wasn’t ovulating I was not getting any progesterone and therefore had cycles with unopposed estrogen.
I’ve been treating women who have hypoestrogen levels and have seen the dramatic changes that occur when estrogen and progesterone are replaced in a cyclic dosing schedule and reach their individual therapeutic range in the blood serum. Like I said earlier, estrogen peaks around 350-550 pg/ml and is around 100-150 pg/ml on baseline days. Progesterone peaks around 10-15 ng/ml and is around 2-5 ng/ml on baseline days. Hormones that are too low cause symptoms that women feel and experience. They are real symptoms.
How long would you replace your thyroid if you were hypothyroid? I believe you would say forever. Well, I say that is how long we should replace our estrogen and progesterone if we have hypoestrogen. The results are amazing. It’s easier to replace hormones when receptors are still present and active. But, it is never too late. I have patients who are doing amazingly well that are in their late 70’s. I also have patients as young as 19 whose symptoms are resolved dramatically using bioidentical hormones in cyclic dosing and the results cannot even compare to that of traditional care, which is oral birth control pills (synthetic estrogen and synthetic progestins) given in static doses using low amounts of hormones. I know many women who cannot stand how they feel on the pill. Maybe some women don’t even realize that it is the pill causing some of the symptoms they experience.
Women can change the standard of care. My goal is to educate women and then we have a choice what we want to do with that information. We cycle. Let’s keep on cycling.
Hypoestrogen, What is that?
Lombard (630) 627-3700 to set up an appointment or email me at jones.gretchen@gmail.com
