08 September 2015

I asked Dr. Oliver Bogler, a male breast cancer patient and advocate, to provide his perspective as a male breast cancer patient and cancer researcher. 

Guest post by Dr. Oliver Bogler
The observation published in JAMA Surgery (doi:10.1001/jamasurg.2015.2657) that prophylactic contralateral mastectomies are on the rise in men with breast cancer made a lot of news recently, including on major outlets like Newsweek and the Washington Post. The study, by Dr. Ahmedin Jemal of the American Cancer Society and colleagues, shows that between 2004/5 and 2010/11 the rate of these prophylactic mastectomies rose from 3% to 5.6% – small numbers, but a large relative increase of 86.7% in 6 years. People seem to be wondering why.

By way of a brief background, men make up about 1% of breast cancer patients, and given the relative lack of knowledge about the male form of the disease, they are clinically managed like women with overall good outcomes. Men are typically diagnosed later (older and with more advanced stage) probably because awareness lags behind women and there is of course no screening, but grade for grade we do as well as women. Men can also be predisposed to having breast cancer by BRCA mutations, and are more commonly associated with BRCA2. I’ve written more on the biology of biology of tumor suppressor genes and familial predisposition on my blog and so won’t go into any detail here. Suffice it to say, that as far as we know today, which admittedly isn’t far enough, male breast cancer looks a lot like female breast cancer.

I think it is therefore reasonable to consider whether the reasons why men chose prophylactic contralateral mastectomies are the same that motivate women to make this choice. The report by Jemal and colleagues doesn’t look at BRCA status (data not available) nor does it examine the attitudes that having breast cancer and/or a BRCA mutation inform in people so affected. Excellent work in this latter area is being done by, for example, Dr. Sharlene Hesse-Biber, who has written on women in this context (Waiting for Cancer to Come) and is actively researching men. (Disclosure: I have participated in Dr. Hesse-Biber’s research work as a subject.)

Until we know the full answer of what drives men’s decisions on mastectomy, we can perhaps consider anecdotal evidence: I spoke with a man just last week who made exactly this choice after he learned from the analysis  following his first mastectomy, that he was a BRCA2 mutation carrier. His rationale: same as women. He felt that his remaining breast was not useful and it had an elevated risk of growing a tumor, so why not remove it. Why wait for the tumor to grow first?

I think it is therefore most likely that the increase in genetic testing, particularly for BRCA, is driving the increase in men’s  prophylactic contralateral mastectomies. For women access to affordable, effective reconstruction is probably a contributing plus, but for men this is not likely, as we rarely opt for this choice.

Are the number out of proportion? In the Huffington Post Dr. Jemal is quoted as saying ‘”[The operation] is only recommended for a small proportion of men,” and the rates observed in the new study are higher than this proportion, said Dr. Ahmedin Jemal, vice president of surveillance and health services research at the American Cancer Society and the lead researcher on the study.’  I am not sure I understand this comment. The proportion of men with breast cancer who likely have a BRCA mutation is likely around 5-10%, although we do not yet have very robust numbers on this, I believe. If true, the percentage of men opting for the prophylactic surgery might correspond quite well with the percentage who have a good genetic reason.

Perhaps Dr. Jemal is arguing that it only makes sense to remove the contralateral breast when the stage of breast cancer is considered curable by surgery alone i.e. at stage I or less. Men admittedly are more often diagnosed at stage II, or even III and IV, and by definition we are talking about men with a diagnosis of cancer and already one mastectomy under (over?) their belt i.e. not people who have a predisposition but no cancer diagnosis, like Ms. Jolie. I understand this biologically: if you are stage II and above  the cancer cells are on the move to a greater or lesser extent, and the focus must be on regional control with radiation and systemic control with chemo and hormone therapy, as appropriate. These approaches are aimed at keeping the cells hiding throughout your body at bay. But if we knew where a bunch of likely cells were hiding with a high likelihood, and it was in a very accessible place and in tissue that wasn’t useful, wouldn’t we simply remove them surgically?

Of course the key to this question is data in the form of large cohort studies – ultimately we will want to know whether men with BRCA mutations did better if they had the prophylactic contralateral mastectomies than if they didn’t, both in terms of overall survival and disease free survival. My guess is that it will be a long time before such a study can be done, even retrospectively, in men, so we will look to the women for guidance. Of course over there they haven’t quite agreed on the value of a mammogram yet, so we won’t hold our breath. In the meantime, if it was me (and it isn’t – I do not have BRCA mutations) I would gladly turn the other breast.

Dr. Oliver Bogler is a former cancer researcher and male breast cancer patient and advocate. He writes about his experience and issues related to male breast cancer at Entering a World of Pink

 

24 August 2015

A study published in JAMA Oncology raises more questions regarding appropriate treatments for ductal carcinoma in-situ (DCIS). I wrote about surgery for DCIS about a month ago. The controversy continues.

The JAMA Oncology study by Dr. Steven Narod and colleagues used the SEER Database to try to determine if treatment for DCIS improves the death rate. They found that breast cancer-specific mortality was approximately 3.3% over a 20 year period, a very low rate. Certain patient populations such as women under the age of 40, African Americans, and patients with ER-negative and more aggressive subtypes of DCIS had higher mortality rates.

This study has led to headlines including Doubt is Raised over the Value of Surgery for Breast Lesion at Earliest Stage (New York Times, New Breast Cancer Study Raises Questions, Delivers Few Answers (NBC News), Study Sparks Debate on Treatment for Early Stage Breast Cancer (USA Today) and Early Stage Breast Cancer Not a Death Sentence (WebMD). Evaluation of the news coverage by Health News Review provided some context. Linked below are the comments of several experts.

The scope of the problem is huge. DCIS represents approximately 20-25% of all breast cancers, and about 60,000 women in the US will be diagnosed every year. It is most commonly diagnosed by mammography, as it usually does not form a lump. DCIS is known as “Stage 0” breast cancer – under the microscope, the cells look the same as invasive cancer cells, but they are contained within the milk ducts. DCIS has been considered a non-obligate precursor to invasive cancer (may turn into but doesn’t always). A less common point of view considers DCIS to be a “high risk” lesion indicating an increased risk of developing breast cancer in the future. Since we don’t have a good way to determine which lesions simply indicate high risk and which ones will progress, we generally recommend surgery, radiation therapy, and hormonal therapy (such as tamoxifen or aromatase inhibitors, if the DCIS is hormone-receptor positive) with the goal of reducing the risk of invasive cancer and death. The Narod study is notable in that the researchers found that regardless of whether or not women received radiation therapy, survival rates did not change. If DCIS is a direct precursor to invasive cancer, treatment that reduces recurrence rates should result in improved survival.

What is very clear is that DCIS is not one disease, and we haven’t yet gotten to the point of being able to pin this down for the individual woman. Some forms of DCIS may indeed simply be markers of increased risk. Lifestyle changes, hormonal, or immunological therapies could potentially be used to reduce the risk of invasive cancer in these cases, a point raised by Drs. Laura Esserman and Catherine Yau in their JAMA Oncology editorial: Rethinking the Standard for Ductal Carcinoma In Situ Treatment. Some women may ask, “what is the harm in treatment?” or “isn’t it better to be sure?”. But surgery, radiation therapy and hormonal therapy are associated with long term side effects such as pain, breast fibrosis and scarring, lymphedema, osteoporosis and more.

There are some limitations of the study. It was a database review, not a prospective randomized trial, which is considered the “gold standard” for research. While the researchers report on 20-year mortality rates, these are projected, not actual rates – women were followed for variable amounts of time, depending on when they were diagnosed and entered into the database. Other factors such as family history and presence or absence of a genetic mutation were not evaluated.

Research is clearly needed in multiple areas including the biologic behavior of the various subtypes of DCIS as well as racial, ethnic and age-related differences related to tumor behavior. In the meantime, women newly diagnosed should keep in mind that we do not have all the answers. A careful case-by-case evaluation is necessary to help come up with the most appropriate treatment plan, based on our current knowledge and an individual woman’s preferences. A diagnosis of DCIS is not an emergency. Take your time to become informed before making your decisions.

To be continued…

Expert Opinions:
How Should we Treat Stage 0 Breast Cancer Dr. David Gorsky
Why Women and Doctors Need to Know More About DCIS Dr. Elaine Schattner
Treatment for Early Breast Cancer will Benefit Some Dr. Otis Brawley
Are All Appearances What They Seem? New Insights into DCIS Dr. Susan Love
What the Headlines Got Wrong About The New DCIS Study Oncology Times
How Do We Treat Early Stage Breast Cancer The Diane Rehm Show (NPR) with Drs. Barnett Kramer, Shawna Willey, Vinay Prasad and Daniel Kopans

31 July 2015

The majority of patients newly diagnosed with breast cancer are candidates to undergo what is known as breast conserving surgery, or lumpectomy. However, one challenge is obtaining a clear margin – a rim of normal tissue around the tumor. While we have gotten better at visualizing the extent of the tumor by using mammograms, ultrasound and MRI, none of these modalities can detect microscopic cancer cells. We know that a large or wide margin of normal tissue is no longer necessary, but we do aim for a margin clear of cancer cells to reduce the risk of recurrence. If the final pathology demonstrates that a surgical margin is positive (contains cancer cells at the edge of the tissue that was removed), it is generally recommended that the patient undergo another lumpectomy, known as a re-excision.

While there are various techniques to help reduce the rate of positive margins, re-excision rates can range from less than 10% to 50% or more, depending on the institution and the study. The American Society of Breast Surgeons recently convened a consensus conference to address this issue. The CALLER (Collaborative Attempt to Lower Lumpectomy Re-Operation Rates) Workshop evaluated various methods that surgeons can use to help reduce the rate of re-excision, and the results were published today in the Annals of Surgical Oncology.

Some of the techniques agreed upon to reduce repeat surgery rates were:

  • Minimally invasive (needle) biopsy rather than surgery to make the initial diagnosis
  • Multidisciplinary discussions prior to surgery including surgery, medical oncology radiation oncology, pathology and radiology
  • Specific surgical techniques to identify non-palpable (not able to be felt) tumors
  • Oncoplastic surgical techniques when appropriate to allow removal of larger areas of tissue and still have a good cosmetic result
  • Marking the different tumor margins (specimen orientation) – essentially marking “which way is up”
  • X-ray of the tissue removed in cases of non-palpable tumors, with surgeon review of the images
  • Consideration for “shave margins“, a technique where additional tissue is taken after the lumpectomy
  • Evaluation of the tissue removed by the pathologist in the operating room
  • Compliance with existing guidelines regarding the appropriate margin size

Re-excision rates shouldn’t be zero. Removing a larger amount of breast tissue often results in a worse cosmetic result. An acceptable rate is probably less than 20%. It is very reasonable for patients to ask their physicians what their average re-excision rate is prior to undergoing a lumpectomy.

9 June 2015

Surgery doesn’t help women with early-stage breast cancer – that’s certainly a headline that will get attention. The recent NPR article referred to a study published in JAMA Surgery: Survival Benefit of Breast Surgery for Low Risk Ductal Carcinoma In Situ – A Population-Based Cohort Study(1). The study raises some very interesting points, but the NPR headline is misleading. Early stage breast cancer can refer to Stages 0, I, and 2, and the study cited only refers to low grade ductal carcinoma in situ.

In this study, researchers used the SEER database to identify fifty seven thousand cases of DCIS treated in the United States from 1988-2011. 2% of that group did not undergo surgery. The researchers evaluated breast cancer specific survival in the patients treated with and without surgery in relation to tumor grade. They concluded that there was no survival advantage to undergoing surgery in cases of low grade DCIS. For patients with intermediate grade DCIS, 10 year breast cancer specific survival rates were 98.6% in the group who underwent surgery vs 94.6% in the non-surgical group. For patients with high-grade DCIS, 10 year breast cancer specific survival was 98.4% in the surgical patients vs. 90.5% in the non-surgical group.

Ductal carcinoma in-situ is also referred to as noninvasive, or Stage 0 breast cancer. It is primarily diagnosed by screening mammogram, as it often does not form a palpable lump. DCIS accounts for approximately 20% of all breast cancers detected by mammography. As screening mammography has become more prevalent, the rate of DCIS detection has increased. Since DCIS does not always progress to invasive cancer, it is a very reasonable for a newly diagnosed woman to ask “Do I need surgery?”.

A hallmark of cancer is the ability to invade surrounding organs and metastasize, and whether or not DCIS should even be considered “cancer” has been the subject of much debate. Dr. Laura Esserman and others have suggested that DCIS be re-classified as an Indolent Lesion of Epithelial Origin(2). The traditional therapy for DCIS is surgical excision (lumpectomy or mastectomy depending on the extent of disease), radiation therapy, and hormonal therapy such as tamoxifen if the DCIS is estrogen receptor positive. The concern of Dr. Esserman and many others is that we are overdiagnosing and overtreating many women. It is estimated that approximately 25-50% of cases of DCIS will likely progress to invasive disease – 60% over 10 years for high grade vs 16% for low grade (1). Preventing invasive disease, which carries a possibility for metastasis, is the primary goal when treating DCIS.

Unfortunately, we are not yet in a position to accurately predict which cases of DCIS will progress and which will not. The study by Sagara et al categorized the DCIS by tumor grade, and this is an important factor in predicting biologic behavior. However, as was pointed out by Margenthaler and Vaughan in their commentary No Surgery for Low Grade Ductal Carcinoma In Situ? (3), a detailed tumor genomic analysis such as the 12-gene assay provides more comprehensive information about tumor behavior and prognosis. Currently this assay is being used in selected cases to classify DCIS as low, intermediate and high risk and to guide treatment. Another limitation of the Sagara study is the retrospective nature, so that information regarding surgical margins and other factors known to be important in recurrence rates is not known. In addition, only 2% of the patients with DCIS underwent non-operative therapy, so the sample size is very small. It is also not known why some women did not undergo surgery.

An additional concern regarding nonoperative therapy is that if surgery is not performed, the diagnosis depends on the accuracy of the core biopsy. In approximately 15-20% of cases when DCIS is found on core biopsy, the surgical pathology actually demonstrates invasive cancer (4). As the entire lesion cannot be sampled with needle biopsy, we don’t know if we are actually observing an invasive cancer.

So can surgery be avoided in women with early stage breast cancer? My answer is in selected cases possibly, but more information is needed. Several ongoing trials will hopefully provide some answers. In the United States, the ALLIANCE trial involves treating patients with letrozole for 3-6 months prior to surgery with tumor assessment by biopsy and MRI. A similar study is being performed at the University of California San Francisco using either tamoxifen or letrozole prior to surgery. Both studies are evaluating tumor biomarkers to help determine if response can be predicted based on specific tumor factors.

In Europe, 2 non-operative trials are opening – LORD and LORIS. Both will include patients with low-grade DCIS and randomize them to either active surveillance or treatment.

We are anxiously awaiting the results of these studies. Identifying women who do not benefit from treatment is an important question that needs to be answered. However at this time, we do not have enough information to make the general recommendation of active surveillance for all women with low grade DCIS.

References:
1. Sagara Y, et al. Survival Benefit of Breast Surgery for Low Grade Ductal Carcinoma In Situ: A Population-Based Cohort Study. JAMA Surg Published online June 03, 2015.;():. doi:10.1001/jamasurg.2015.0895.
2. Esserman LJ, et al. Overdiagnosis and Overtreatment in Cancer: An Opportunity for Improvement. JAMA 2013:310(8)797-798
3. Margenthaler JA, Vaughan A. No Surgery For Low-Grade Ductal Carcinoma In Situ? JAMA Surg Published online June 03, 2015. doi:10.1001/jamasurg.2015.0895
4. Kumiawan ED et al. Risk Factors for Invasive Breast Cancer when Core Needle Biopsy Shows Ductal Carcinoma In Situ.
Arch Surg 2010;145(11)1098-1104

30 March 2015

Annual Report to the Nation on the Status of Cancer, 1975-2011, Featuring Incidence of Breast Cancer Subtypes by Race/Ethnicity, Poverty and State

Today, the Journal of the National Cancer Institute (JNCI) released a report reviewing cancer data, specifically breast cancer, from 1975-2011. For the first time, data regarding breast cancer subtypes was included in the report, and incidence of breast cancer subtypes by age, race/ethnicity, poverty level, and other factors are included. The following summarizes some of the information found in the report.

It is well known that breast cancer is not one disease. There are 4 primary molecular subtypes based on hormone receptor (HR) status (commonly reported as ER / estrogen receptor and PR / progesterone receptor) and Her2/neu status. The subtypes are:
– Luminal A: HR+ / Her2 negative; 72% of all breast cancers
– Luminal B: HR+ /  Her2 positive; 10% of all breast cancers
– Her2-enriched: HR- / Her2 positive; 5% of all breast cancers
– Basal-like / Triple Negative: HR- / Her2 negative; 13% of all breast cancers

The report demonstrated that there are some unique patterns breast cancer subtype related to race/ethnicity, poverty level, and geography.
– HR+ / Her2- breast cancer is considered to be the least aggressive subtype. Rates of this subtype were highest in non-Hispanic white women. The rates of this breast cancer subtype decreased with increasing poverty levels for every racial and ethnic group. This subtype of breast cancer also correlated strongly with use of screening mammography.

– In women younger than age 45, HR+ / Her2 negative breast cancer rates are comparable among racial / ethnic groups, but for older women this subtype was seen more often in non-Hispanic white women.

– Non-Hispanic Black women had the highest rate of HR- / Her2 – (triple negative) breast cancer, which has been known for some time. However, as triple negative breast cancer is less common than HR+ / Her2 negative disease, more women had the latter subtype. The report also confirmed that this population had the highest rates of late-stage disease and of poorly differentiated pathology (indicates more aggressive tumor behavior)  regardless of molecular subtype, and the highest rate of breast cancer deaths.

Overall trends in incidence and death rates from cancers were also noted in the report. Lung cancer remains the leading cause of death among both men and women. Black men had the highest cancer death rate of any racial or ethnic group. Lung, prostate and colorectal cancers were the leading causes of cancer death among men except in the Asian / Pacific Islander group where the leading causes were lung, liver and colorectal cancer.

Among women, the leading causes of death were found to be lung, breast and colorectal cancers. For both men and women, death rates for the 3 most common cancers declined. Exceptions were American Indian / Alaska Native men, lung cancer in Asian / Pacific Islander women (stable death rate) and colorectal cancer in American Indian / Alaska Native women (stable death rate). Death rates for liver, pancreatic, soft tissue and uterine cancers as well as melanoma were also reported. There are racial / ethnic differences present for these types of cancer as well.

There are many factors contributing to cancer incidence and death rates including race / ethnicity, socioeconomic status, geographic location and more. Reporting cancer incidence by subtype will give more insight into population-based factors, and will hopefully lead to innovative solutions  to the growing problem of disparities in cancer incidence and outcome.

Additional information from the National Cancer Institute.

28 January 2015

A study published in the journal Cancer found that many women lack basic knowledge about their breast cancer. Researchers at the Dana Farber Cancer Institute in Boston surveyed 500 women treated between 2010-2011 for Stage 0 – III breast cancer in Northern California. Women were asked about 4 tumor characteristics – estrogen receptor (ER) status, Her2/neu status, tumor grade and disease stage.

They found that overall, 55% reported knowing their ER status, 33% reported knowing their Her2/neu status, 82% reported knowing their disease stage, and 32% reported knowing their tumor grade. 14% reported knowing all characteristics, and 14% reported knowing none.

However, patient perception of knowledge did not reflect actual knowledge. Only 8% answered all questions correctly. They also found that African American and Hispanic women had a lower rate of stated knowledge and correct answers. Differences in education and health literacy were associated with less knowledge about one’s own condition, but controlling for these factors did not eliminate the observed differences for minority participants.

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The findings are important for several reasons. As the authors noted in their manuscript, “having knowledge about one’s health conditions or the risk of developing health conditions can promote healthy behaviors and treatment adherence. Better general knowledge about cancer is associated with cancer screening, earlier stage at presentation and survival, and enhanced satisfaction with care.” “Improving a patient’s understanding about why a particular treatment is important to her individual situation may lead to more informed decisions and better adherence to treatment plans.”

While it is generally felt that breast cancer patients are highly educated about their disease, this study shows that as physicians, we have a long way to go. We need to do a better job assessing a patient’s understanding of their disease and treatment options, and we need to design and participate in research studies that evaluate new and innovative ways to explain complicated information to a newly diagnosed breast cancer patient taking into account education level as well as racial, ethnic and cultural differences. Our discussions need to be tailored to the individual patient. And patients should feel empowered to ask questions and obtain clarification in order to fully understand the treatment recommendations and the rational behind those recommendations.

Reuters News Coverage

19 January 2015

This past weekend, I gave a talk at the Southern California Chapter of the American College of Surgeons Annual Meeting – the title of the talk was Increasing Mastectomy Rates – Science vs. Personal Choice.

There is a tremendous amount of literature documenting the increasing mastectomy rates. The talk focused on women with early stage breast cancer at average risk for developing a recurrence or new cancer – women without a BRCA gene mutation. As has been my practice for several years when giving a talk which includes the patient experience, I asked you for input, and received a lot of information. The following is a summary of the talk, including your perspective.

The use of mastectomy for breast cancer has been documented as early as the 1500s, despite the fact that general anesthesia did not come into use until the 1840s. Sir William Halsted described the radical mastectomy, which involved removal of the breast, all of the overlying skin, the pectoral (chest) muscle, and a significant number of lymph nodes. It was a very aggressive surgery but at the time, many women at the time presented with advanced disease – cancers that grew through the skin or chest muscle. The Halsted theory was that if the breast and lymph nodes could be removed with an extensive “en bloc” surgery, the cancer had a lower likelihood of spreading. However, despite this aggressive approach, the dismal survival rates from breast cancer did not improve.

Halsted died in 1922, but the radical mastectomy remained the surgical procedure of choice until the 1960-70s. The landmark NSABP B04 trial, led by Dr. Bernard Fisher, demonstrated that regardless of surgical decision (radical mastectomy vs. total mastectomy – no removal of the muscle) the survival rates were equivalent, and these results have held up for 25 years(1). The Fisher theory was that cancer may be metastatic from the beginning, and that a more extensive surgical procedure would not be expected to improve survival rates. The NSABP B06 trial demonstrated equivalent survival rates whether women underwent mastectomy, lumpectomy / radiation, or lumpectomy alone. However, if radiation therapy was not performed, the risk of local recurrence (cancer returning in the breast) was 39.2%, compared to 14.3% with radiation(2). This is the basis for our current recommendation of lumpectomy followed by radiation therapy for early stage breast cancer. A 1990 NIH consensus panel stated that “breast conservation treatment is an appropriate method of primary therapy for the majority of women with early-stage breast cancer and is preferable because it provides survival rates equivalent to those of mastectomy while preserving the breast’’(3).

This was seen as a major scientific advance, and one that was embraced by patients – no longer did women need to have a breast removed for early stage disease, and from the early to mid 1990s, lumpectomy rates started increasing while mastectomy rates decreased.

The Women’s Health and Cancer Rights act of 1998 stated that if an insurance company covered the procedure of mastectomy, they were required to cover reconstructive surgery, including procedures performed on the other breast to produce a symmetrical appearance, as well as prosthetics for lymphedema. This set the stage for immediate reconstruction, which prior to this time was generally not performed (or recommended) on a regular basis.

We think of the “Celebrity Effect” when we hear Angelina Jolie, Amy Robach, and others discuss their decisions. But in 1987, Nancy Regan underwent a mastectomy for breast cancer, and she received a significant amount of criticism for her decision, both from the medical community as well as from advocacy groups. Women who underwent breast cancer surgery from the end of 1987 to early 1988 were 25% less likely to undergo lumpectomy compared to earlier in 1987, prior to her diagnosis(4). Lumpectomy rates subsequently increased, but she later wrote “This is a very personal decision, one that each woman must make for herself. This was my choice, and I don’t believe I should have been criticized for it”(5).

Around 2004, it was noted that mastectomy rates started rising(6). This trend was seen nationally as well as in many individual institutions.

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In addition to an increase in mastectomies being performed for early stage breast cancer, an increase has been seen in contralateral prophylactic mastectomy – removal of the other, non-cancerous breast. Many studies have been published confirming this trend, and also evaluating factors associated with an increased mastectomy rate(7,8,9). They include:
– Young age, Caucasian race
– Higher economic status, better insurance, availability of reconstruction
– Family history of breast cancer or genetic testing – even if the genetic testing was negative
– Undergoing an MRI, even if the MRI was normal

Patient factors have also been evaluated. Many studies have cited that women make their decisions out of fear. Interestingly, there seems to be some intellectual disconnect – women report that they understand there is no improvement in survival, yet state that they made their decision “to live longer”. The physician has been identified as a very important source of information, yet only 1/3 of women stated that a desire to follow their physician’s recommendation was important in making their decision. Many women over-estimate their risk of developing a new breast cancer – some reporting they think their risk is as high as 50%. Other studies have reported that women make their decisions to gain a sense of control over cancer, but that many have an exaggerated sense of control, stating that they are making the decision “so I don’t have to go through this again”, while admitting that they are aware that mastectomy does not reduce the rate of metastatic disease. The impact of a family member / friend experience was also noted to be very important. All of us make decisions in our daily lives based on personal experience rather than hard facts – a woman facing a decision about breast cancer surgery is no different. Finally, many woman remain very satisfied with their decision even 20 years after the surgery. However, it is important to note that 10-30% report issues related to self-esteem, body image, sexuality, emotional stability, and overall quality of life (10, 11, 12).

Some facts(10, 13, 14, 15):
– For women at average risk of breast cancer (BRCA negative) the rate of developing a new breast cancer is approximately 0.5 – 0.75% per year. This can be reduced if the women undergoes chemotherapy and/or endocrine therapy
– Mastectomy for early stage breast cancer or contralateral prophylactic mastectomy does not reduce the likelihood that breast cancer will metastasize (spread to other areas of the body)
– The complication rate increases with more surgery – bilateral mastectomy is associated with 30-40% risk of complications including infection, fluid accumulation, and re-operation.

So what did you, the #BCSM Community have to say? Out of those who responded:
– “I knew survival rates were the same” – most patients well informed, had surgeons who presented all sides, supported their decision
– 40% said decisions influenced by family/friend experience
– 15% had lumpectomy initially, then opted for bilateral mastectomy after anxiety of repeat imaging and biopsies.
– 6 patients: lumpectomy and radiation: significant problems with wound healing, fibrosis and later underwent a mastectomy
– 5 patients subsequently developed metastatic disease; no regrets on their decision
– 3 patients required multiple surgeries due to revisions, infection, lost implant – no regrets
– 2 patients felt pushed into their decision, one by family members and another by their physician – both regretted their decision

There are a lot of comments on the original blog post; here are a few I received by email:
– “I wish doctors, researchers and the media understood (some do) – there are many valid reasons for choosing a mastectomy, even with the state-of-science today”
– “The focus is on ‘simple’ surgery – the potential toxicity of radiation therapy is grossly minimized. While serious and long-term side effects of radiation therapy may be rare, they do occur. It is ironic now that patients have a choice in treatment selection, there is so much hand-wringing by the medical establishment in the choices that many women make”
– “We are diligent. We are thoughtful. We have good reasons for choosing the “big surgery”. Our doctors explain the risk factors, we process the information, we understand the full ramifications of our choice, and are still confident that this is the right choice for our set of circumstances.
– It may not fit the medically necessary criteria, but it may fit with the emotionally necessary criteria. I hear your evidence based science and I’ll raise you five intangibles…”

So what is the answer? Clearly physicians have a responsibility to educate our patients not only on the lack of overall survival benefit, on the complication rates. Physicians also need to do a better job of assessing and explaining a patient’s risk of developing a recurrence or a new breast cancer. And patients should be encouraged to take their time, obtain opinions, and carefully consider all options prior to making a decision. But rather than irrational fear, what many of see in our practice is “Reasonable Fear”. Patient’s biases and personal experiences need to be acknowledged. Some bias, but not all, can be overcome with education. But until science advances to allow us to truly predict who will and will not develop a recurrence or a new breast cancer, personal choice should remain an option.

References:
1. Fisher B et al. 25 Year follow up of a randomized trial comparing radical mastectomy, total mastectomy, and total mastectomy followed by irradiation. NEJM 2002;347 (8)
2. Fisher B et al. 20 Year follow up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer NEJM 2002;347 (16)
3. NIH Consensus Conference: Treatment of Early Stage Breast Cancer. JAMA 1991 265
4. Nattinger AB, et al Effect of Nancy Regan’s mastectomy on choice of surgery for breast cancer by US women. JAMA 1998 (279) 10 762-766
5. Olson, J: “Bathsheba’s Breast: Women, Cancer and History” The Johns Hopkins University Press 2002
6. McGuire KP, et al Are mastectomies on the rise? A 13 year trend analysis of the selection of mastectomy versus breast conservation therapy in 5865 patients. Ann Surg Oncol 2009 16:2682-2690
7. Mahmood U, et al Increasing national mastectomy rates for the treatment of early stage breast cancer. Ann Surg Oncol 2013 20:1436-1443
8. Yao K, et al Trends in contralateral prophylactic mastectomy for unilateral cancer: A report from the national cancer database 1998-2007. Ann Surg Oncol 2010(17) 2554-2562
9. King TA, et al Clinical management factors contribute to the decision for contralateral prophylactic mastectomy. J Clin Oncol 29:2158-2164 97-200
10. Rosenberg SM, et al Perceptions, knowledge and satisfaction with contralateral prophylactic mastectomy among young women with breast cancer Ann Intern Med 2013;159:373-381
11. Covelli AM, et al ‘Taking control of cancer’: Understanding women’s choice for mastectomy.  Ann Surg Oncol DOI 10.1245/s10434-014-4033-7
12. Frost MH, et al Contralateral prophylactic mastectomy: Long term consistency of satisfaction and adverse effects and the significance of informed decision making, quality of life, and personality traits. Ann Surg Oncol 2011 18:3110-3116
13. Fayanju O et al Contralateral prophylactic mastectomy after unilateral breast cancer: a systematic review and meta-analysis. Ann Surg 2014; 260:1000-1010  
14. Roberts A et al Cost effectiveness of contralateral prophylactic mastectomy for prevention of contralateral prophylactic mastectomy. Ann Surg Oncol 2014 21:2209-2217
15. Miller ME et al  Operative risks associated with contralateral prophylactic mastectomy: A single institution experience. Ann Surg Oncol 2013 204113-4120.

23 November 2014

Guest Post by Dr. Oliver Bogler

When thinking about a post on male breast cancer, one person came to mind –  Dr. Oliver Bogler. As a cancer researcher, Dr. Bogler has a very unique perspective on his diagnosis, treatment, and the larger problem of research disparities when it comes to male breast cancer. Here is his guest post: 

My personal encounter with breast cancer started with my diagnosis in September of 2012. My story is very typical. As I have written more extensively about it elsewhere let me be brief: I felt a lump, and after a few months of denial I had it checked out, and then very quickly was diagnosed and treated at MD Anderson Cancer Center in Houston, where I also work. More on that below, but let’s first look at some facts about the male disease.

About Male Breast Cancer
Approximately one in every hundred people diagnosed with breast cancer is a man. That’s about 2,200 new cases a year in the USA. Men have breasts, meaning that they have the same lobular glands and ducts that women have, though they have less tissue and it does not produce milk. Accordingly, male breast cancer is typically ductal carcinoma and hormone receptor positive and Her2 negative, which is also the most common type of breast cancer in women. Men are diagnosed later in life, typically, with a median age at diagnosis of 68, or about 7years older than women. For that reason men also present more often with more advanced forms of breast cancer – stages III and IV are more common, and stage I very rare. One possible explanation is that a lack of awareness results in delayed diagnosis, and so more advanced presentation at a later age.

Treatment regimens for men are essentially identical to those used for women, and outcomes are very similar, as far as we know. Because male breast cancers are typically hormone receptor positive, hormone therapy with the anti-estrogen tamoxifen is commonly an important part of the therapy. It suppresses male estrogen, and thereby other hormones also, which are co-regulated, including testosterone.

Many websites, including those of the American Cancer Society and the National Cancer Institute provide fundamental information about male breast cancer. Interventional clinical trials on breast cancer that men are eligible for can be found here (ClinicalTrials.gov is a registry and results database of publicly and privately supported clinical studies of human participants conducted around the world).

My advice: if you feel a lump, any lump, go see a doctor right away.

My Journey – Our Journey
One of the reasons I hesitated to get my lump checked out was that my wife had been diagnosed and treated for breast cancer about 5 years before me. I couldn’t really grasp the improbability of it hitting our nuclear family twice. Being Irene’s care taker and then a patient allows me to say with confidence that the treatments for men and women are identical: we both had up-front chemotherapy in a two step regimen: 12 rounds of weekly Taxol and then 4 rounds of the combination FAC at three week intervals. MD Anderson physicians prefer to give the chemo first as it provides an opportunity to see how the tumor responds. Then we both had surgery – modified radical mastectomy with axillary lymph node dissection – followed by 6 weeks of radiation to the chest wall. Now we both take hormone therapy – aromatase inhibitors for Irene, good old tamoxifen for me. Evidently we feel that marriage is all about sharing experiences 🙂

What we know about male breast cancer and opportunities to learn more
What do we know? Probably not enough. I do accept that the treatment men receive is effective – there are some relatively small-scale, hospital registry based studies showing this. When adjusted for age and stage at diagnosis, it looks like men do as well as women with today’s approaches. On the other hand, the possibility that a sex-hormone driven cancer may have important differences between men and women cannot be excluded. Very encouraging is a current, larger registry trial in a network of European and US cancer centers with about 1,200 men that will provide a robust baseline outcomes data set and afford the opportunity to collect tissue and study the disease. It is the kind of research that was being done 20+ years ago in women.

An analysis I wrote about on my blog and in Breast Diseases Quarterly [Bogler, O. (2013) Male Breast Cancer: Opportunities for Research and Clinical Trials. Breast Diseases: A Year Book Quarterly 24(3), 216-218] suggests that there is very little primary research on the male disease. There are no laboratory models, cell lines or other tools. Few if any grants supporting this kind of fundamental biology are in evidence, and aside from the inclusion of male breast cancer in the epidemiology of rare cancers it is hard to find any support for research from the National Cancer Institute or foundations. Given that the NCI alone spends $600M on breast cancer research, there is in my mind ample opportunity to dedicate some to this question. Perhaps 1% would be a good start?

On a similar note, men are only eligible for about 30% of breast cancer clinical trials found on clinicaltrials.gov, suggesting that access is a real issue. Of course in some instances our inclusion may not make sense, but I believe that in many instances inertia rather than a biological rationale underlies the exclusion of men. Both of these areas provide significant opportunities to learn more about the male disease and how best to deal with it clinically.

The Awareness Gap
Being a man with what is widely understood to be a women’s cancer leads to some dissonant experiences. To me these are mostly mildly funny, and not an issue – being asked how I get a mammogram for instance (the same way you do…), or filling out a form that asks me whether I am pregnant or when my last period was. Its fine – I get it. Mostly women here, and mostly the men in the waiting room aren’t wearing the medical arm band. But having breast cancer as a man is still (local) news worthy, and has modest shock value – that is surprising. The issue here is that a lack of awareness is probably a contributing factor to the delayed diagnosis in men and that means in some cases in their earlier death. It is certainly contributing to the underfunding of research and exclusion of men from trials. We need to change that.

A key challenge for men with breast cancer is the phenomenal success of the breast cancer awareness community. While the excesses of “pink” are unfortunately common these days, I do acknowledge the amazing work the community has done, and am deeply grateful for it. Alone the fact that we can have frank, open discourse about breast cancer, any cancer, is a tribute to the brave women who came out with their disease in the past 50 years. Then, the mobilization of public and private resources for awareness, screening and research is a tremendous accomplishment. And the US is a clear leader in this – a significant cultural accomplishment. But if this huge silver lining has a tiny, tiny black cloud it is that pink leaves almost no room for awareness about men. Breast cancer actually is not a sex-specific cancer like ovarian, uterine, testicular or prostate – it just appears to be. A great illustration of this phenomenon for me is the NFL players who in October don pink in support of women with breast cancer (hurray!) and completely fail to take the opportunity to also mention that they themselves could be diagnosed with this disease one day (booo!).

I want to close by being clear: I am not advocating for male breast cancer at the expense of other forms of breast cancer. Not at all. I want it to have its place with, and alongside. And in proportion – 1% would be a good start. Perhaps my concerns are not dissimilar from those of the inflammatory, triple negative or metastatic breast cancer communities: being outside the pink mainstream presents awareness challenges, which in turn make it harder to gain the resources needed to change the fate of many women and men with breast cancer.

 Dr. Oliver Bogler is a cancer researcher, male breast cancer patient, and male breast cancer advocate. His blog can be found at Entering a World of Pink.

15 July 2014

A study published today in Clinical Cancer Research demonstrates that tamoxifen applied to the skin in a gel form was as effective as oral tamoxifen in decreasing breast cancer cell growth and was associated with fewer side effects in patients with ductal carcinoma in-situ (DCIS).

Dr. Seema Kahn and colleagues randomized 27 women diagnosed with DCIS to receive either tamoxifen gel or oral tamoxifen for 6-10 weeks prior to surgery. They measured blood and breast tissue concentration of tamoxifen as well as the proliferative activity (growth rate – also known as Ki67) of breast cancer cells before and after treatment. They found that both forms of tamoxifen resulted in a decrease in the growth rate of cancer cells. Both groups showed similar concentrations of tamoxifen in the breast tissue, but the women who used the gel had lower tamoxifen concentrations in the blood.

Tamoxifen is used to treat breast cancer and is also used to reduce the risk of developing breast cancer in those at high risk. In women who have been diagnosed with breast cancer, tamoxifen can reduce the risk of cancer returning and can improve overall survival rates. However, many studies have shown that women often stop tamoxifen due to side effects. Those side effects can include vaginal discharge and exacerbation of menopausal symptoms such as hot flashes, sleep and mood disturbance, depression, and weight gain. The two most significant potential complications related to tamoxifen use are uterine cancer and blood clots. The study was too small to note any difference in side effects, but as the concentrations of tamoxifen in the blood are lower in patients using the gel, it is thought that this might result in fewer side effects.

This was a small study and many questions remain, but it is promising that an effective form of tamoxifen associated with fewer side effects may be eventually be available for widespread use.

** 6 December 2018 – Editor’s Note:
The NSABP B-39 clinical trial results were recently presented at the San Antonio Breast Cancer Symposium. This study compared 3 forms of radiation therapy. After 10 year followup, approximately 4% of patients who underwent whole-breast irradiation after lumpectomy developed cancer recurrence in the same breast. This is lower than what was quoted below (10-15%, point #3) which was based on older data. This new study demonstrates that the recurrence rate after lumpectomy and radiation (4%) is nearly equivalent to that of mastectomy (1-3%).

3 June 2014

A study was recently published evaluating the reasons why women diagnosed with breast cancer might undergo a contralateral prophylactic mastectomy. First, some definitions:
–       Mastectomy – removal of the entire breast
–       Prophylactic mastectomy – removal of a breast that does not have cancer
–       Contralateral prophylactic mastectomy (CPM) – removal of the breast that does NOT have cancer, in a patient undergoing mastectomy for cancer on the other side

The study, which was published in JAMA Surgery, concluded that “Many women considered CPM and a substantial number received it, although few had a clinically significant risk of contralateral breast cancer. Receipt of magnetic resonance imaging at diagnosis contributed to receipt of CPM. Worry about recurrence appeared to drive decisions for CPM although the procedure has not been shown to reduce recurrence risk. More research is needed about the underlying factors driving the use of CPM.”

Some background information:
1.  Over 25 years’ worth of data exists showing that long-term survival is equivalent whether a woman undergoes a lumpectomy or a mastectomy:  In other words, you will not live any longer if your breast is removed.

2.  There is no difference in the likelihood of metastatic disease (spread outside the breast – most commonly bones, liver, lung and brain) whether you have a lumpectomy or mastectomy.

**see editor’s note, above. 
3.  Lumpectomy followed by radiation therapy (this is also called breast conservation therapy, or BCT) generally has low rates of “in breast recurrence” or “in breast new primary” – low rates of the original cancer coming back in the same breast, or a new cancer developing in the same breast.  These rates are historically about 10-15%, although these rates are likely reduced with modern adjuvant antihormonal, radiation, and chemo- therapies.

4.  Even though much more breast tissue is removed (~99% of breast tissue cells) mastectomy is still associated with a 1-3% risk of cancer recurrence at the site of breast removal.  This is usually in the skin or muscle.

5.  CPM is associated with a 20-40% complication rate, especially unplanned additional surgery

6.  The average woman’s risk of developing a new cancer in the opposite breast is approximately 0.5-1% per year. If a cancer develops in the contralateral (other) breast, it is considered a “new primary” – a whole new breast cancer. Even though it might be the same type as the original cancer, it is generally not considered a recurrence. If the original cancer is estrogen / progesterone receptor positive, taking tamoxifen or aromatase inhibitors can reduce the risk of cancer returning after a lumpectomy, and can reduce the risk of a new cancer developing in the other breast. However, lumpectomy or mastectomy for the original cancer does not alter the rate of new breast cancer development.

7.  Women who carry a BRCA gene mutation have a 60-80+% lifetime risk of developing breast cancer in either breast, and a high risk of developing a new breast cancer, so bilateral mastectomy is often recommended. These patients are generally excluded from the discussions regarding whether or not CPM is a reasonable option due to their extremely high risk.

Over the past 20 years, research studies have supported a “less is more” approach to breast cancer surgery such as: BCT,  narrower margins of normal tissue removed around cancer, and less extensive lymph node removal. Before instituting these changes, studies were done to ensure that less aggressive surgery does not impact long-term survival rates. Despite these advances, there has recently been a steady increase in the rate of mastectomy, as well as CPM.  In article after article, physicians are scratching their heads.  The use of MRI, inadequate education, unrealistic expectations from reconstructive surgery, the “celebrity effect”, as well as fear and anxiety have been blamed.

The “new” study and our thoughts:
The recent study in JAMA Surgery focused on a small subset of women (8%) from a national database that elected CPM as part of treatment for unilateral breast cancer.  The authors reported that of 106 patients who received CPM, “80% indicated it was done to prevent breast cancer from developing in the other breast,” leaving only 21 patients (1.5%) from their sample of 1447 surveyed women that elect CPM for reasons other than the prevention of the development of a new contralateral breast cancer.  However, the author’s conclusions ignore this and direct the reader’s attention instead to patients’ concern for recurrence, stating, again, that “worry about recurrence appeared to drive decisions for CPM.”

The problem with this type of analysis is this:  when ‘patient fear’ is discussed, it frequently is implied by the reporting media that hysterical women are running to the operating room to be unnecessarily operated on by uneducated surgeons.

Judging the merits of a surgical procedure or treatment on the fact that few women “are likely to experience a survival benefit,” is not reflective of the complexity of the treatment decision-making process for women with a new diagnosis of breast cancer.  Faced with a multitude of decisions to make in a short time frame, it is not surprising that many such patients will report anxiety concerning recurrence.

The truth is simple:  surgical choice is a combination of factors. There is little doubt that some physicians do not spend the time needed to hear the concerns of their patients and respond to them appropriately. Conversely, some patients do not want to hear all of the facts, preferring simply to opt for what seems the “safest” approach, even though the science says otherwise.

What we see in our offices is a rational fear: Many women understand that the type of surgery does not determine their survival.  While of utmost importance, survival is not the only thing that is important to women being treated for breast cancer. Women worry about having to repeat the whole process in another year or so if something new shows up on a mammogram or if a lump is felt. Women question the value of annual mammography for surveillance when their initial tumor was not picked up by a mammogram. Women have seen their family members and friends develop complications from radiation therapy and from attempts to perform additional surgery after radiation therapy. While women understand that a mastectomy is no guarantee that they will remain cancer-free, to many it is such a significant decrease in the rate of recurrence or new primary cancer that they feel it is an acceptable trade off for the complication rates that have been reported in patients who undergo a CPM with reconstruction.  Physicians also agonize over the decision.  Properly educated patients are in the best position to make decisions regarding their own breast health care, but even the best education does not alleviate all anxieties, nor can it eliminate all risk.

Physicians and researchers talk about the increasing rate of CPM as a crisis. But the real crisis is that at this point, we simply do not have options for women that they are comfortable with. Unnecessary surgery is a concern for patients and physicians. However, until we can look a woman in the eye and give her more accurate information about her individual risk of recurrence or new primary disease, it is our opinion that the decision for CPM should be between a woman, her family, and her physicians.

Additional Reading:
JAMA Editorial: Contralateral Prophylactic Mastectomy – An Opportunity for Shared Decision Making
Medscape Article – Misconceptions and Fear Prompt Contralateral Mastectomy
The Patient Perspective: Blog Post by Catherine Guthrie

Deanna J. Attai, MD
Michael S. Cowher, MD