10 December 2017

A study published in the New England Journal of Medicine has shown that birth control pills and other forms of hormone based contraception (such as some intrauterine devices (IUDs) are associated with an increased risk of breast cancer. We’ve thought that the pills currently in use, which have much lower doses of estrogen and progesterone compared to older formulations, did not have a significant impact on breast cancer risk. However, the study showed a small but increased rate of breast cancer developing in those using birth control pills and IUDs.

The large study (1.8 million women), performed in Denmark, evaluated the breast cancer risk in women under the age of 50. The breast cancer risk associated with hormonal birth control is small – out of 100,000 women, there was an increase of 13 breast cancers per year (68 / year in the hormonal contraception group and 55 per year in the non-users). Most of the cases that occurred in this study were in women in their 40s. In women under the age of 35, the increased risk was 2 cases per 100,000 women.  As limitation of the study is that it did not take into account other breast cancer risk factors such as breast feeding history, alcohol intake, and exercise patterns. Breast cancer risk increased with duration of contraceptive therapy. It is important to note that as this was an observational study, it cannot conclusively be stated that hormonal contraception causes breast cancer – only that it is associated with an increased risk.

The increased risk needs to be balanced against the potential benefits of hormonal contraceptive therapy, such as preventing unwanted pregnancy, control of heavy bleeding especially during the perimenopausal period, and reduction in the subsequent risk of ovarian, endometrial and (possibly) colorectal cancers. Potential risks of long term hormonal contraception include an increased incidence in blood clots (especially in women who are overweight and/or smokers) and stroke.

Patients should evaluate their risk tolerance, breast cancer risk factors, and the risks and benefits of hormonal contraception in their individual case. As expected, the media coverage on the story is variable – HealthNewsReview.org did a good job of evaluating the media coverage and summarizing the important points of the study.

Additional Information:
NEJM Editorial
NPR – Even Low Dose Contraceptives Slightly Increase Breast Cancer Risk 
NY Times – Birth Control Pills Still Linked to Breast Cancer Risk
NY Times – Birth Control and Breast Cancer – Putting the Risk into Perspective

10 November 2017

The American Society of Clinical Oncology (ASCO) has just released a statement on alcohol and cancer. They note that the importance of alcohol consumption as a contributor to cancer development is under appreciated, and that in the US, approximately 3.5% of all cancer deaths are related to alcohol intake. While the association between alcohol intake (especially heavy consumption) has been known for some time, this is the first formal statement from ASCO on the subject. Alcohol intake is most strongly linked to head and neck, esophageal, liver, colon and breast cancers.

Moderate drinking is defined as one alcoholic drink per day for women and two per day for men. The greatest risk appears to be in those who drink heavily, although there does not appear to be a “safe” level of intake. In a New York Times article, Dr. Clifford Hudis, the chief executive of ASCO, noted that “The more you drink, the higher the risk. It’s a pretty linear dose-response”. ASCO did not recommend that people stop drinking altogether, but they did suggest that more education for both oncology providers and the public is needed about the relationships between alcohol consumption and cancer.

Of course, people who never drink alcohol can still develop cancer, and some who are heavy drinkers will not. Alcohol intake is just one of many lifestyle factors that can contribute to increased risk. And as Aaron Carroll writes, also in the New York Times, “maybe any increase in risk is too much for you”. If you do drink, I recommend that women limit their alcohol intake to 3-6 drinks per week – and don’t save up your weekly allowance for Friday or Saturday night! I think Dr. Carroll’s conclusion stated it best: “The absolute risks of light and moderate drinking are small, while many people derive pleasure from the occasional cocktail or glass of wine. It’s perfectly reasonable even if a risk exists — and the overall risk is debatable — to decide that the quality of life gained from that drink is greater than the potential harms it entails.”

8 May 2017

As a past-president of the American Society of Breast Surgeons I am probably more than a little biased. However, as always, the annual meeting held April 26-30th in Las Vegas was terrific. Topics including the full spectrum of breast disease, including benign and high risk lesions, genetic testing, breast cancer diagnosis and treatment including medical and radiation oncology updates, and metastatic disease.

The press briefing highlighted 3 abstracts which showed that:

  • Modern therapy for inflammatory breast cancer is associated with better outcomes than historically seen
  • Post-treatment lymphedema is related to a combination of treatments including surgery, radiation therapy, and chemotherapy – not just from surgery
  • Patients with DCIS have a 5 year risk of developing a cancer in the other breast of 2.8% and a 10 year risk of 5.6%, and patients should be discouraged from undergoing bilateral mastectomy for this condition. Developing a new cancer in the previously treated breast was twice as likely as developing a new cancer in the opposite breast, and the use of tamoxifen reduced the likelihood of any recurrence.

Dr. Nathalie Johnson moderated a pre-meeting course on Building a Breast Cancer Survivorship Program. I was invited to speak on Traditional Versus Virtual – Options for Patient Support and Education. Just as it can be challenging to choose between cake and ice cream (2 really good things), patients note advantages to both in person and online support and education. It doesn’t have to be one or the other – do what works for YOU! My slides are posted on SlideShare.

During the general sessions, a few topics stood out to me:

Dr. Shelley Hwang from Duke University spoke on DCIS subtyping and overtreatment. She noted that DCIS now comprises over 20% of all mammographically detected breast cancer. It is considered a “non-obligate precursor” of invasive cancer – the rate and likelihood of progression to invasive cancer are not clearly known. However, it is clear that some patients will never exhibit progression to invasive disease, and she discussed this in the context of thyroid and prostate cancer – two situations where we know that treatment in some patients will not provide the patient any benefit. The challenge is to sort out which patients will benefit from treatment and which ones will not. The COMET study is currently enrolling patients with low grade DCIS to in an attempt to help answer these questions.

Dr. Virginia Herrmann from Washington University in St. Louis spoke on non-genetic breast cancer risk factors. This is an important topic and I believe one that doesn’t get covered enough. She noted that hormone replacement therapy does increase risk – although the incremental risk is small and is seen only after about 5 years of use. However, longer term use does result in higher risk. Increased body mass index (BMI) is associated with risk – the risk of breast cancer is 30% higher in patients with a BMI greater than 31 kg/m2 compared to a BMI of 20 kg/m2. She noted that there is a linear relationship between alcohol intake and cancer risk, noting a 10% increase in risk for each 10 gm/day (for wine this is a little over 3 oz) increment in alcohol consumption. The risk is most associated with post-menopausal breast cancer, although in the study she quoted, only alcohol intake during age 50s was associated with an increased risk of postmenopausal breast cancer. She noted the association of ionizing radiation and breast cancer, and young women who received mantle (chest area) radiation for Hodgkin’s lymphoma have a markedly increased risk for developing breast cancer. She noted that breast cancer risk is increased in smokers, correlated with smoking intensity and duration. Finally, she noted the increased risk of breast cancer among soldiers stationed at Camp LeJune related to contaminated drinking water (tetrachloroethylene and trichloroethylene).

Dr. Tiffany Traina, a Memorial Sloan Kettering medical oncologist, gave a brief presentation about triple negative breast cancer: Searching For the Magic Bullet. There are several promising treatment strategies including targeting androgen receptors, the use of PARP-inhibitors in patients who have BRCA gene mutations, antibody-drug conjugates, immune modulating approaches, and targeted therapies based on tumor genomic profiles. Stay tuned – much more to come over the next few years related to this aggressive breast cancer subtype.

Dr. Lisa Newman, from the Henry Ford Health System in Detroit, spoke on Breast Cancer Outcomes: Disparities versus Biology. I have heard her speak on this topic multiple times over the years and always enjoy her excellent presentations. She noted that the incidence of breast cancer in black women is increasing, now close to that in white women. However, mortality rates for black women are higher than those for white women. There is an increased frequency of triple negative breast cancer in black women. She is involved in a research initiative evaluating the association between African ancestry and high risk breast cancer in white American women, African American women, and women in Ghana, including studying novel aspects of tumor biology and breast cancer stem cells – she is asking the question “are there differences in the oncogenic potential of mammary tissue that are associated with ancestry”? She concluded with what I felt was a powerful slide – 60% – 43% – 20%. Those were the survival rates for passengers on the Titanic who were in 1st – 2nd – 3rd class. She noted that healthcare outcomes are often dependent on access to care, and ended with a quote from Dr. Martin Luther King, Jr.: “Of all the forms of injustice, inequality in health care is the most shocking and inhumane”.

Dr. Stephen Edge, from the Roswell Park Cancer Institute, gave an update on the new American Joint Commission on Cancer staging system (AJCC 8th edition). Currently we stage breast cancer based on tumor size and lymph node status. However, it is recognized that that tumor biology plays an important role in prognosis and in some patients it may be more important that tumor size. The new staging system will incorporate tumor grade, Her2/neu status, ER/PR status, and Oncotype Dx status (if available) and should more accurately reflect prognosis. There are 422 lines in the new staging system – it will be impossible to memorize! Thankfully, he noted that the AJCC is working on a staging app.

The last day of the meeting held some great sessions, and the meeting room remained packed up until the very last minute. Dr. Ann Partridge from Dana Farber discussed special considerations in the young breast cancer patient. She noted that the disease is different, the patients are different, and the treatments should be different. Younger women have a higher likelihood to have more aggressive subtypes such as Her2/neu over-expressed and triple negative, and have lower survival rates than older women – even in those with the ER positive breast cancer. However, she cautioned not to over-treat patients based only on age. She noted that young age is not a contraindication for breast conservation, and that there is no clear improvement in mortality in patients who undergo more extensive surgery. She noted the need for improvements in treatment and support, including focused research and guidelines, which should lead to better outcomes.

Dr. Irene Wapnir from Stanford spoke on fertility preservation issues. She noted the various fertility options including medications and procedures. She also reviewed the POSITIVE trial, which will be assessing the risk of breast cancer relapse in patients who temporarily stop endocrine therapy to permit pregnancy, as well as to evaluate factors associated with successful pregnancy after interruption of endocrine therapy. She also stressed that fertility preservation should be discussed with any woman of childbearing age, whether or not she has had a prior pregnancy or a child – physicians won’t know what is important to their patients unless we ask!

Dr. Katherina Zabicki Calvillo from Dana Farber discussed breast cancer in pregnancy. She noted that 0.2-4.0% of breast cancers are diagnosed in pregnant patients – about 1 in 3000 pregnancies. She also noted that given the overall delay in childbearing (and the association of increasing age with breast cancer), the incidence of pregnancy-associated breast cancer will increase. Delays in diagnosis are related to hormonal changes which affect breast tissue making the exam more challenging, and that many patients and physicians assume that masses are related to pregnancy. She stressed that pregnancy termination is usually NOT required, but a multidisciplinary team approach is required. Many of these patients present in more advanced stages, but stage-for-stage, the prognosis is similar to non-pregnant patients with breast cancer. Chemotherapy can be given after the first trimester, but hormonal and Her2/neu targeted therapy should be avoided. She noted that mastectomy should be performed in the first and early 2nd trimester, and discussed the challenges of immediate reconstruction. Breast conservation could be considered in the late 2nd or 3rd trimester with post-lumpectomy radiation planned for after delivery.

Dr. Kevin Hughes from the Massachusetts General Hospital reviewed research studies that have found that in women over the age of 70 with early stage breast cancer, radiation therapy after lumpectomy may not be necessary.  The CALGB 9343 study showed that survival rates were the same whether women received radiation therapy or not. Radiation therapy did reduce the likelihood of cancer returning in the breast (local recurrence) from about 4% in the untreated patients to about 1% in the treated patients (after 5 years of follow up). However it is important to realize that the majority of women in that study were treated with endocrine therapy, which can help reduce the risk of local recurrence. As with many decisions regarding breast cancer treatment, a careful discussion of the risks and benefits of each option is necessary.

Dr. Tina Hieken from the Mayo Clinic gave a very interesting talk on the microbiome and the impact on breast cancer. We normally co-exist with many bacteria – we have ten times the more microbial cells compared to human cells. These microbes carry out metabolic reactions that can be essential to human health. The genetic material (genome) of our microorganisms is called the microbiome. She and her colleagues studied breast tissue from women with and without breast cancer and found that the background breast microbiome is different in women with breast cancer compared to those with benign conditions. She concluded by noting that the future may involve using a microbial pattern to predict breast cancer risk, exploiting the microbiome to enhance treatment response, and that there may also be implications for a cancer prevention vaccine. The Washington Post recently covered her research – definitely worth a read for more information.

Dr. Anthony Lucci from MD Anderson discussed the “Ongoing Saga of Circulating Tumor Cells”. We would all like to see the day when a blood test can tell us with certainty if cancer has developed or returned – but we’re not there yet. After reviewing several studies evaluating both circulating tumor cells (CTC) and circulating “cell free” DNA, he concluded that this information does provide prognostic information in both metastatic and non-metastatic patients, but is not in the current ASCO or NCCN guidelines for guiding treatment. Combining the CTC status with response to preoperative chemotherapy may identify a low risk subset of patients, but noted that additional studies are needed before we can reach the ultimate goal which is improving outcomes by monitoring and responding to CTC and cell free DNA levels.

Dr. Manjeet Chadha from Mount Sinai spoke on repeat lumpectomy after prior lumpectomy and breast radiation. Traditionally, mastectomy has been recommended if cancer returns after lumpectomy and radiation therapy. On average, there is about a 10% risk of “in breast” recurrence after lumpectomy and radiation, but this will vary based on tumor and treatment type. She reviewed several studies evaluating the different types of focused or partial breast radiation that may be used in selected patients who experience recurrence of their breast cancer. She also called for additional studies in this area.

One of the last talks was by Dr. Mehra Golshan from Dana Farber. He spoke about the decision whether or not to operate on patients with breast cancer who present with Stage IV (metastatic) disease. Traditionally, we have not recommended surgery for patients with metastatic breast cancer as these patients were not expected to have long survival, and it was not felt that removal of the main tumor would impact survival. Evaluating existing studies has also been challenging because while some have shown a benefit to removal of the main tumor, the patients who underwent surgery in those studies tended to be younger and healthier. He concluded by noting that surgery in patients with Stage IV breast cancer is not standard of care, but some studies do support this practice. It is recommended that these patients be evaluated in a multidisciplinary forum and that treatment choices be individualized.

 I returned from the meeting exhausted but energized. In addition to the scientific content, the meeting is an opportunity to connect with friends and colleagues across the country. I’m already looking forward to ASBrS 2018!

This post has not been endorsed by the American Society of Breast Surgeons.

23 August 2016

A study published in the Annals of Internal Medicine evaluated screening mammography taking into account breast density and breast cancer risk. For women age 50-74, the conclusion of the authors was that for women of average risk with low breast density (fatty or scattered fibroglandular), triennial (every 3 year) mammography screening averted the same number of breast cancer deaths as annual or biennial screening. Women screened every 3 years also had lower rates of biopsy procedures. For women at high risk with high breast density (heterogeneously or extremely dense), annual screening was better. High risk / high density patients accounted for approximately 1% of the study population.

The study was funded by the National Cancer Institute. The authors used simulation modeling which included national breast cancer incidence, breast density, and screening performance data. They did not include patients with genetic abnormalities such as BRCA 1/2 mutations. They also did not take into account the impact of MRI or tomosynthesis / 3D mammography.

Risk assessment involves a calculation (using various models) which takes into account a woman’s age, body mass index, menstrual and reproductive history, family history, prior biopsies, and other factors known to influence the risk of breast cancer development. In the current study, the authors used a risk calculator that takes into account breast density. Breast density is a factor associated with breast cancer, although studies vary regarding the impact of density on risk. Adding to the confusion, breast density rating is subjective – different radiologists may assign different density scores to the same patient. The model used in the current study also takes into account factors such as improved detection using digital mammography, improved treatment effectiveness, and the usual decrease in breast density that is seen with increasing age. It is unclear at this time which is the “best” risk assessment model to use – all have limitations, some significantly over-estimate risk, and none are a “crystal ball”.

So what should women do? The ideal screening test is one that is inexpensive, readily available and safe. It should also find cancers early enough to make a difference. Mammograms are an imperfect tool but they perform reasonably well in a wide variety of settings. The ideal screening program is to tailor the technology and screening frequency to the patient’s risk – one size never fits all. Women should be aware of their family history and risk factors, ask about their breast density, and then discuss these factors as well as their personal preferences regarding breast cancer screening with their physicians. True individualized and personalized risk-based screening is not yet a reality, but by making recommendations based on risk, we are taking steps in the right direction.

14 September 2015

A study just published in JAMA Internal Medicine found that a Mediterranean diet (MeDiet) supplemented with extra virgin olive oil (EVOO) was associated with a lower rate of breast cancer.

Dr. Miguel Martinez-Gonzalez and co-authors were studying the effects of dietary interventions in men and women at high risk of cardiovascular disease. While the study was not initially designed to evaluate the effects of dietary interventions on the rates of breast cancer, the authors reported on some interesting findings.

Men (age 55-80) and women (age 60-80) at risk for cardiovascular disease (due to diabetes or at least 3 of the following: smoking, hypertension, elevated LDL, low HDL, overweight, obesity, family history of premature cardiovascular disease) in Spain were randomized to a MeDiet supplemented with EVOO (one liter per week for the family), a MeDiet supplemented with mixed nuts (30 grams / day), or a control diet (advice to lower overall fat intake).

During a median follow up of 4.8 years, 35 cases of malignant breast cancer were demonstrated in 4282 women. Breast cancer information was not available for 122 of the women. Women in the MeDiet + EVOO group had a 62% lower incidence of breast cancer compared to the control group (68% reduction when controlled for age, body mass index, exercise and alcohol intake). Women in the MeDiet + nuts group had a non-significant reduction in breast cancer incidence compared to the control group. The women who had the lowest incidence of breast cancer consumed at least 4 tablespoons of EVOO per day.

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There are several limitations to this study. Participants were white postmenopausal women, living in Spain, at risk for cardiovascular disease, so the study results may not apply to other populations. The rates of breast cancer observed in the study are very low, and we do not know if women had mammograms or if all were free from breast cancer at study enrollment. Also, while the relative risk reduction was significant, the actual risk reduction was less so: 2.9 women per 1000 / year in the control group developed breast cancer. 1.8 / 1000 / year developed cancer in the MedDiet + nuts group, and 1.1 / 1000 / year developed cancer in the MedDiet + EVOO group.

While the polyphenols and other compounds in EVOO have been shown to have certain anti-cancer effects in some cell culture studies, it is very premature to suggest that EVOO alone will prevent the development of breast cancer. The MeDiet is high in mono-unsaturated fats (EVOO, nuts, fish, and lean meats), low in saturated fats and dairy, and high in vegetables and fruits. While olive oil is one component of a healthy diet, total caloric intake, saturated fat intake, and quantity of vegetables and fruits consumed are all important. Simply adding olive oil to a diet that is otherwise unhealthy or adding olive oil to a diet that contains more calories than appropriate is unlikely to improve overall health or reduce the rate of breast cancer development.

Dr. Mitchell Katz, in an editorial accompanying the study, noted that despite the study limitations, the MeDiet “… is known to reduce the risk of cardiovascular disease and is safe. It may also prevent breast cancer.” My recommendation based on this and other studies is not to simply supplement your current diet with olive oil, but evaluate your entire diet. Look at your current sources of fat, your current intake of fruits and vegetables, as well as total caloric intake. Olive oil may or may not turn out to be a “magic” ingredient, but many of us can benefit from incorporating components of the MeDiet into our daily routine.

Additional information on diet and lifestyle

14 May 2013
BRCA gene testing and prophylactic mastectomy were thrust into the spotlight when Angelina Jolie announced in May 2013 that she tested positive for a BRCA mutation and underwent preventative surgery. The interview below discusses who should be tested, and some of the issues to consider regarding prophylactic surgery.

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15 January 2013

Much has been written regarding the role of soy and breast cancer, but much confusion remains. While research in this area is active, here is what we know:

Soy is an isoflavone, a class of chemical that has weak estrogen-like activity.  We know that women in Asian countries, following a traditional diet, have a lower incidence of breast cancer than women in the US. Their diet consists of large quantities of soy foods starting at a young age. However they eat soy in a natural form – they do not eat “foods” such as soy hot dogs or take soy in supplement form. Research has shown that consuming large quantities of natural soy products starting at a young age seems to confer some estrogen resistance to the breast tissue, which may account for the lower incidence of breast cancer in the Asian population.

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8 November 2012

I had the honor to collaborate on this ASCO Connection post with Dr. Don S. Dizon, a medical oncologist at the Massachusetts General Hospital specializing in women’s cancers.  This post grew out of twitter and email conversations  – we were discussing cancer prevention, risk reduction, and cure – and how our conversations and thoughts have changed due in part from our interactions with patients in the  BCSM Community and other social media sites.

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