19 December 2018

A study recently published in the Annals of Internal Medicine noted that breast cancer risk increases after childbirth, peaking at about 5 years after delivery. The increased risk was seen to persist for over 20 years.

The Annals study pooled the results from 15 prospective series. They found that in women with prior pregnancy, who had their most recent child 3 – 6.9 years before the study period, there were 41 excess breast cancer cases per 100,000 women at age 45, 170 excess cases per 100,000 at age 47.5, and 247 per 100,000 women at age 50. These numbers, while statistically significant, are relatively low. However, they may of course be considered important to an individual woman, deciding whether or not to have children. 

The authors discussed that proliferation of breast cells during pregnancy and the post-partum microenvironment may play roles in facilitating and promoting abnormal cellular proliferation and mutation. There was a protective (not preventative) effect of breast feeding. In addition, as this study conflicts with prior research noting a protective effect of pregnancy in terms of breast cancer development, the authors suggest that this protective effect may relate more to breast cancer that develops at the “peak ages” (after 60) rather than in younger women.

As this study was a pooled analysis of other studies, information on breast feeding was not available for all patients, there were some patients where it was not possible to distinguish if breast cancer developed during pregnancy or during the immediate postpartum period, and there was limited data on breast cancer subtypes.

The impact of pregnancy on recurrence risk in patients who have been treated for breast cancer is an area of active research. A 2013 study demonstrated that patients who became pregnant after being treated for an estrogen-receptor positive breast cancer did not have increased risks of cancer recurrence. In addition, there is an ongoing cooperative group clinical trial, the POSITIVE study, evaluating outcomes of women who have been treated for breast cancer and then interrupt endocrine therapy treatment for pregnancy.

My take-home points from the Annals study are that there seems to be an association (which is very different from cause and effect) between pregnancy and development of breast cancer at a young age, but the absolute number of increased breast cancer cases are relatively small. I do not think this study should discourage women from starting a family if they want to have children, and the authors have not recommended enhanced breast cancer screening for women who have been pregnant. All women are at risk for breast cancer, and pregnancy may increase short term risk. Of course, any new breast finding or change should be evaluated, whether a woman has had children or not. 

Additional Information:
HealthLine -Women Have Higher Risk of Breast Cancer After Childbirth
NY Times-Breast Cancer Risk May Rise After Childbirth, but is Still Low

10 December 2018

Being overweight after menopause is associated with an increased risk of breast cancer. But a new study suggests that our traditional measure of overweight, the body mass index (BMI) may not tell the whole story.

A recent study, published in JAMA Oncology, performed detailed body composition analysis on 3000 women who were of normal BMI. They found that among these women, those with increased levels of body fat (especially in the truncal area – “belly fat”) had higher risks of estrogen receptor positive (ER+) breast cancer compared to women with lower body fat levels. In addition, the women with higher body fat levels also had higher levels of inflammatory markers as well as other metabolic abnormalities. 

This suggests that maintaining a healthy weight may not be enough. Muscle mass declines with age, so even if weight is stable, there is a slow but steady increase in body fat. Regular exercise can certainly help to maintain muscle mass and it also helps decrease the level of inflammatory markers. 

The authors note that more study is needed to better understand the links between body fat and breast cancer, but it is very clear that there is no way around it – exercise is essential for good health.

Additional Information:
NBC News: Belly fat increases risk of breast cancer despite normal BMI
CNN – Body fat levels linked to breast cancer risk in post-menopausal women

10 May 2018

The American Society of Breast Surgeons held their Annual Meeting in Orlando, FL from May 2nd – 6th. As usual, it was well attended – the meeting is known for being very practical and full of information that breast surgeons can bring back to their practices to help improve patient care.

I’ve picked a few topics to highlight in this post: Genetics, Imaging, Local Therapy, Systemic Therapy, Immunotherapy, Liquid Biopsy, Diet and Hormone Therapy, and Changing Paradigms. The following are comments expressed by the meeting speakers. My own comments will be noted in bold italics.

Genetics:

  • BRCA 1 mutation carriers are more likely to have triple negative breast cancer.
  • BRCA 2 mutation carriers are more likely to have ER positive, Her2/neu negative breast cancers.
  • The risk of a 2nd breast cancer in BRCA mutation carriers on average is about 2% per year depending on the specific mutation and the age of affected relatives. It can approach 60-80% in some patients. This increased risk of a new breast cancer is why bilateral mastectomy is often recommended. Removal of the opposite breast may result in improved overall survival but results from studies are mixed.
  • For BRCA mutation carriers, it is recommended that clinical breast exam (breast exam by the physician) be performed every 6-12 months. From age 25-29 annual MRI is recommended, and from age 30-75 annual mammogram (3D mammogram or tomosynthesis was recommended) along with MRI was recommended. It was stated that this screening regimen has not been shown to improve survival, but the screen-detected cancers were less likely to have lymph node involvement. No specific recommendation was made for imaging or exam after bilateral mastectomy.
  • MRI every 6 months has been suggested by some, but there are concerns about gadolinium (a heavy metal material which is the contrast agent used for breast MRI) buildup.
  • Removal of the ovaries is recommended around age 40.
  • In patients with BRCA mutations who undergo salpingo-oophorectomy (removal of the ovaries and fallopian tubes), estrogen replacement therapy has not been shown to increase subsequent breast cancer risk. However, combined estrogen / progesterone therapy may increase subsequent breast cancer risk. It was suggested to consider removing the uterus at the time of ovary removal, so that estrogen alone could be used (if the uterus is not removed, estrogen alone could increase the risk of uterine cancer).
  • There are many other genetic mutations that have been identified that have a variable association with increased breast cancer risk. It was stressed that family history and other factors need to be considered when these less common mutations (such as CHEK2, ATM, PALB2 and many more) are present, before recommending mastectomy.
  • It was stressed that the presence of a variant of unknown significance (VUS) should NOT prompt aggressive surgery.
  • A study was presented that demonstrated that current breast cancer genetic testing guidelines exclude almost half of high-risk patients, and a recommendation was made for testing of all breast cancer patients regardless of age, family history or other factors.

Breast Imaging:

  • Dense breast (as determined by mammogram) reduces the sensitivity of mammograms, and also is associated with an increased risk of breast cancer.
  • It was stressed that determination of breast density is subjective and studies have shown significant variability in grading of breast density. Automated methods of assessing density are being evaluated.
  • 34 states have dense breast notification legislation. Some have supplemental screening (such as ultrasound) legislation (California does not).
  • An advantage of tomosynthesis (also known as 3D mammogram) in patients with dense breasts is that it decreases the likelihood of callbacks and improves the cancer detection rate
  • Abbreviated (3 minute scan) MRI shows promise for screening.
  • There is an ECOG/ACRIN study planned which will evaluate abbreviated MRI versus tomosynthesis in women with dense breasts.
  • Contrast-enhanced mammography is superior to digital mammography but it requires an IV contrast dye, and there is currently no ability to biopsy lesions seen only with this technique.
  • It was stressed that automated whole breast ultrasound (ABUS) should not replace mammography.
  • Molecular breast imaging has a much higher radiation dose due to the need to inject a radioactive material and cost is higher than other imaging modalities. There are only about 100 units in the US.
  • In addition to BRCA mutation carriers, patients who have a history of chest wall radiation at a young age (most commonly for treatment of Hodgkin’s lymphoma) or those who have a lifetime risk of breast cancer over 20% (assessed by various computer modes) should have annual MRI in addition to mammograms for surveillance.

Loco-Regional (breast and underarm lymph nodes) Therapy:

  • Recurrence of cancer in the breast (known as a local recurrence) was previously thought to be related to “disease burden” – the amount of tumor and size of clear margins. According to Dr. Monica Morrow, this has led to an “obsession” with margins, wider surgical resection than necessary, and the overuse of MRI.
  • Due to improvements in systemic therapy (chemotherapy and endocrine therapy), local recurrences have decreased over time.
  • Local recurrences are largely a function of tumor biology – more aggressive tumor types are more likely to recur. Bigger surgery does not overcome bad biology.
  • The rates of contralateral (opposite side) new breast cancer have been decreasing in the US; currently <1% at 5 years for patients who do not have a genetic mutation.
  • Updated 2018 ASTRO guidelines endorse hypofractionation (a shorter course of radiation therapy) in a larger group of patients.
  • There are 3 trials that will evaluate whether or not radiation therapy can be avoided in selected patients – LUMINA, IDEA and PRECISION.
  • ~30% of patients undergoing “direct to implant” reconstruction (no temporary tissue expander) need a second surgery. One of the plastic surgeons that I work with notes that “reconstruction is a process not a procedure!”
  • Managing expectations of the reconstruction process is important so patients don’t get frustrated and feel like their reconstruction has “failed.”
  • Post mastectomy radiation worsens outcome from implant reconstruction; severe capsular contracture occurs in about 30% of patients.
  • If radiation is performed on the permanent implant instead of the tissue expander, the rate of reconstruction failure goes down by 50%.
  • Many plastic surgeons prefer that autologous (patient’s own body) reconstruction be performed after radiation to avoid shrinkage of the flap. A tissue expander could be placed at the time of mastectomy which will be removed after radiation when the flap procedure is performed.
  • Lymphedema risk is about 25% with axillary node dissection versus 6-8% with sentinel node biopsy. In certain patients over age 70 with ER+ breast cancer, sentinel node biopsy can be avoided – this was also covered in the Society of Surgical Oncology’s Choosing Wisely statements. However, it is also important to take into account whether or not the patient will be treated with radiation and/or endocrine therapy. Sentinel node biopsy is also not recommended for most patients undergoing lumpectomy for DCIS. The SOUND trial is evaluating the use of axillary ultrasound to try to determine if this can help select patients who do not need sentinel node biopsy.

 Systemic Therapy:

  • The use of genomic tumor testing could avoid the use of ineffective (for the specific patient depending on tumor profile) chemotherapy in up to 50,000 patients per year.
  • Neoadjuvant (before surgery) chemotherapy is most commonly used to decrease tumor size so that patients have a higher likelihood of being able to undergo lumpectomy instead of mastectomy.
  • About 50% of patients who have positive lymph nodes before chemotherapy are converted to node-negative due to chemotherapy prior to surgery, and they may be able to avoid full axillary node dissection.
  • Response to neoadjuvant chemotherapy varies by tumor subtype. Her2/neu and triple negative breast cancers are more likely to respond compared to ER+ and Her2/neu negative tumors.
  • Technical considerations to improve the accuracy of sentinel node biopsy after neoadjuvant chemotherapy including the use of 2 dye agents to map the nodes and removal of at least 3 lymph nodes.
  • A multidisciplinary approach for management of patients who are being considered for neoadjuvant chemotherapy was stressed.
  • Recurrence patterns are different for ER+ versus ER- disease. Patients with ER+ breast cancer are at risk for late recurrence, even 20 years after treatment – the highest risk is in patients with multiple involved lymph nodes. Patients with ER- disease tend to recur earlier (within the first 2-5 years), and then the likelihood of recurrence decreases.
  • Recurrence in the breast is a marker of increased risk for development of metastatic disease.
  • Premenopausal patients who have “low risk” disease could consider stopping tamoxifen after 5 years. It is recommended that patients with “high risk” disease consider 10 years of tamoxifen therapy.
  • Postmenopausal patients who are considered “high risk” could consider 10 years of an aromatase inhibitor, although there is not currently data that shows this approach improves survival. Prolonged therapy in these patients does reduce the likelihood of developing a new breast cancer and reduces the likelihood of breast cancer recurrence.

Immunotherapy / Liquid Biopsy:

  • A brief session was held covering immunotherapy and liquid biopsy.
  • Immunotherapy for breast cancer has not had the success seen in melanoma, lung cancer, colon cancer and bladder cancer.
  • The combination of chemotherapy and a modified herpes virus has shown some promise in patients with triple negative breast cancer.
  • It is likely that immunotherapy treatments will vary depending on tumor subtype.
  • Circulating tumor DNA may predict metastatic disease 8-12 months before evidence of tumor spread – but we are not yet able to improve patient outcomes based on this information. Therefore, circulating tumor cell and circulating cancer cell DNA assessments are not recommended for routine clinical use.
  • It was predicted that “liquid biopsy” will eventually be used routinely to help manage breast cancer patients.

 

Diet and Hormone Replacement Therapy:

  • A low fat diet improved the likelihood of death from breast cancer only in obese women.
  • Currently there is more information regarding the impact of dietary fat versus dietary sugar on breast cancer risk. Dr. Rowan Chlebowski, who has been a lead author on the Women’s Health Initiative studies, stated that due to an increasing number of reports suggesting that sugar may impact breast cancer development, they plan to look more closely at this.
  • Insulin resistance is associated with cancer specific and all-cause mortality in postmenopausal women.
  • One of Dr. Chlebowski’s conclusions was to “avoid body fatness.” Unfortunately, specific guidance on how to best accomplish this was not discussed!
  • The risk of breast cancer associated with hormone replacement therapy (HRT) is greater if it is started around the time of menopause versus 3-5 years later.
  • Breast cancer risk in women taking HRT is higher in women with extremely dense breast versus fatty replaced breasts. The biggest risk from HRT is in lean women with extremely dense breasts. The lowest risk from HRT is in women with a body mass index (BMI) > 35 with fatty replaced breasts.
  • Combination estrogen / progesterone HRT should be avoided in lean (BMI <25) women especially if they have dense breast tissue.
  • The Black Women’s Health Study found no increased breast cancer risk if HRT use was <10 years, but cancer risk was increased if use was >10 years. Other studies showed either no risk or no association of risk from HRT with race.

 

Changing Paradigms – Avoiding Surgery for DCIS and Neoadjuvant Patients

  • Active surveillance is being evaluated for ductal carcinoma in-situ (DCIS). Over 60,000 cases of DCIS are diagnosed per year in the US. Not all cases of DCIS will progress to invasive cancer, and the likelihood of progression is lowest in low grade DCIS. In these patients, less than 10% develop invasive cancer in the same breast after 10 years and over 20% die from other causes within 10 years of diagnosis.
  • There are 3 ongoing clinical trials are evaluating active surveillance for low risk DCIS (LORIS, LORD, and COMET). The COMET trial is the only study open in the US. DCISOptions.org has additional information about DCIS and the COMET trial.
  • Some patients who undergo chemotherapy prior to surgery are found to have no residual tumor after the area has been removed, termed pathologic complete response (pCR).
  • Prompted by patients asking “why do I need surgery?” if it appears that all cancer has resolved after chemotherapy, researchers at MD Anderson Cancer Center are evaluating whether surgery can be omitted in patients who appear to have a pCR after chemotherapy. Patients who have no apparent tumor based on post-chemotherapy imaging (including MRI) undergo core needle biopsies. If these biopsies show no tumor, patients taking part in the study will undergo radiation without surgery.
  • Similar studies are taking place in the Netherlands, Germany, and the UK.
  • Henry Kuerer from MD Anderson stated that “surgeons have an obligation to study possibility of no surgery – and we must ensure safety and efficacy with well-designed trials.
  • Several types of ablative therapy (destroying the tumor without surgery) are being evaluated including cryoablation (freezing), laser, and transcutaneous (no needle puncture or scar) high frequency ultrasound.

Lifetime Achievement Award

Dr. Ernie Bodai, the breast surgeon who spearheaded the Breast Cancer Research Stamp, was honored with a lifetime achievement award. It was fascinating to hear his story and how one man (with a little help) got congress to change a law.

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

31 January 2018

In women who undergo lumpectomy for breast cancer, the likelihood of another cancer developing in the treated breast can range from 0.2 – 1.0% per year, and this rate can be decreased with the addition of endocrine therapy such as tamoxifen or an aromatase inhibitor. The likelihood of developing a contralateral (opposite side) breast cancer is about 0.6% per year, and can also be reduced by endocrine therapy. Prior to making a decision on lumpectomy versus mastectomy, women commonly ask about the possible need for additional biopsies and procedures.

A study published in JAMA Surgery reviewed 2 large insurance databases to determine the frequency of breast biopsy after breast cancer treatment. Over 120,000 cases were analyzed. The researchers found that 15-23% of patients underwent subsequent biopsies during the 10 year period evaluated. 20-30% of these patients underwent additional cancer treatment.  Factors associated with lower biopsy rates included the use of endocrine therapy and older age. The use of partial breast irradiation (brachytherapy) was associated with a higher biopsy rate.

As this was an insurance claims database review (review of billing codes, not actual patient charts or medical records), it is not possible to know if biopsies were performed on the side of initial cancer or the opposite side, except in patients initially treated by mastectomy. In addition, a limitation of all claims database studies is that if the billing and diagnosis codes are not correctly entered, the information obtained will not be accurate. However, given the large number of claims reviewed, this study at least provides an estimate for patients to use when weighing the options of lumpectomy or mastectomy.

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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