Posts

21 October 2019

Especially during October, when everything seems to be painted pink, it’s easy to overlook the fact that breast cancer is a disease of women and men. Male breast cancer accounts for 0.6 – 1.0% of all breast cancer cases. In the US, approximately 2600 men will be diagnosed with breast cancer each year. The lifetime risk is about 1 in 1000, versus 1 in 8 for women. Male breast cancer accounts for approximately 500 deaths in the US per year. Risk factors include increasing age, family history including BRCA gene mutations, obesity, alcohol intake, prior chest wall radiation, and low androgen hormone levels.

Male breast cancer tends to be diagnosed in later stages compared with breast cancer in women, and previous studies have come to conflicting conclusions about whether the poorer outcomes are due to higher stage at diagnosis or other factors. A study recently published in JAMA Oncology* looked at mortality rates among men and women diagnosed with breast cancer. The researchers used the National Cancer Database (NCDB) and compared men and women who were diagnosed with breast cancer between January 2004 – December 2014. Their data analysis included approximately 16,000 men and 1.8 million women. Some of the key findings:

  • Mean age at diagnosis was 63.3 for men and 59.9 for women
  • 3-year survival was 86.4% for men and 91.7% for women
  • 5-year survival was 77.6% for men and 86.4% for women
  • Overall survival was 45.8% for men and 60.4% for women

Men diagnosed with breast cancer were older, were more likely to be diagnosed at advanced stages, and were less likely to receive conventional therapy. However, differences in survival persisted even after controlling for clinical characteristics of the disease, age, race and ethnicity, and access to care. Limitations of this study are that cause of death could not be determined (so it is not clear if all of the deaths are related to breast cancer) and the NCDB does not contain information on recurrence, BRCA gene status, adherence to treatment recommendations, and other medical conditions. However, the researchers concluded that male sex remained a significant risk factor for poorer outcomes, which suggests that there are biological differences in male versus female breast cancer. 

Another study recently published in the journal Cancer* also used NCDB information to look at treatment trends for men treated for breast cancer from a similar time period. The authors evaluated approximately 10,000 cases and noted that:

  • 24% underwent breast conserving surgery (lumpectomy)
  • 70% of those undergoing lumpectomy received radiation
  • 44% of patients received chemotherapy
  • 62% of those with estrogen receptor positive (ER+) breast cancer received endocrine therapy
  • 35% of those with ER+ / lymph node negative breast cancer had Oncotype Dx testing on their tumor to help determine need for chemotherapy

These findings are consistent with a point made in the JAMA Oncology study noting that men were less likely to receive conventional therapy – for example only 62% with ER+ breast cancer received endocrine therapy and only 70% of those undergoing breast conserving surgery were treated with postoperative radiation therapy. Some of the same limitations apply to this study, in that reasons for differences in therapy could not be determined, and there was no information on disease recurrence.

A few other important points to make about male breast cancer:

  • Most male breast cancer presents as a lump, but as in women, most lumps are not cancerous. It is important that a proper evaluation (usually including a mammogram and ultrasound, and possibly biopsy) be performed for any change
  • As in women, male breast cancer may present with nipple discharge (especially blood), “puckering” or “pulling in” of the skin, or severe redness of the skin which can be mistaken for infection – the latter may indicate a more aggressive type of breast cancer known as inflammatory breast cancer
  • ALL men with breast cancer, and anyone with a family history of male breast cancer, should undergo genetic counseling and testing. As in women, most cases of male breast cancer are “sporadic” (not related to an inherited mutation), but men with breast cancer are more likely to carry deleterious BRCA (especially BRCA 2) mutations
  • Men who carry a deleterious BRCA mutation have an approximately 8% lifetime risk (to age 80) of developing breast cancer. So while that is considered “high risk” for men, they are still more likely to NOT develop breast cancer. We do not currently recommend prophylactic mastectomy in men who carry a deleterious BRCA mutation but who have not been diagnosed with breast cancer
  • Men who carry a deleterious BRCA mutation are also at higher risk for prostate cancer, melanoma, and pancreatic cancer

Men with breast cancer are usually treated using the same protocols that are used for women. Unfortunately there is limited data to support this. Male breast cancer is not common, so it is challenging to enroll large numbers of patients in clinical trials. However, men have historically been excluded from many breast cancer clinical trials, so how can we even make progress? The US FDA has recently issued draft guidelines encouraging the inclusion of male breast cancer patients in clinical trials – this is certainly a step in the right direction.

*If you are not able to access the full study and would like a copy, please email me: contact at drattai dot com

Additional Information:

3 September 2019

Last week, the US Food and Drug Administration (FDA) issued draft guidelines for industry, which encourage the inclusion of male breast cancer patients in clinical trials that evaluate breast cancer therapies. The guidelines note that “eligibility criteria for clinical trials of breast cancer drugs should allow for inclusion of both males and females” and that “scientific rationale should be included in the protocol when proposing to exclude males from breast cancer trials.” There is a 60-day open comment period on the guideline.

In the US, approximately 2600 men are diagnosed with breast cancer each year, approximately 1% of all new breast cancer cases. Men tend to be diagnosed at more advanced stages compared with women, and there are about 500 male breast cancer related deaths in the US annually. Breast cancer in men is usually treated in a similar manner as in women. However, because men are typically not included in breast cancer clinical trials, it is not known if this is an optimal approach. One of the primary reasons that men are excluded from breast cancer clinical trials is that the disease is uncommon – setting up a vicious cycle where little progress is made. The statement noted that “FDA does not intend to consider low expected accrual rates of male patients with breast cancer to be a sufficient scientific rationale for excluding them from a clinical trial.”

This is most certainly a welcome step towards improving the understanding and treatment of male breast cancer.

17 July 2019

There are no standard guidelines for mammographic screening for men who have no symptoms (such as a lump), even if they are considered to be at high risk for developing breast cancer. A study recently published in Breast Cancer Research and Treatment* evaluated the performance of screening mammography in asymptomatic high risk men.

The researchers reviewed a prospective institutional database at the Memorial Sloan Kettering Cancer Center, evaluating cases from 2011 – 2018. 827 men underwent mammography during that time period, but 80% were excluded from evaluation for this study as they underwent imaging due to the presence of a mass or other symptoms. Data from 163 asymptomatic patients, considered high risk due to a family and/ or personal history of breast cancer or the presence of a deleterious genetic mutation, was analyzed. 

Of the 163 men, 77% had personal history of breast cancer and 44% had a family history of breast cancer. 15% had deleterious BRCA mutations. Most of the genetic mutations (83%) were in the BRCA2 gene, as expected.

Over the 7-year time period, 806 screening mammography examinations were performed. The majority (792 studies, 98%) were BIRADS 1 or 2, indicating a normal study or benign findings. 10 (1.2%) were BIRADS 3 indicating a “probably benign” finding. Upon follow up, all of these patients were considered to have benign findings. 4 men had BIRADS 4 or 5 findings indicating suspicious or highly suspicious findings for which biopsy was recommended, and all were diagnosed with invasive ductal breast cancer.

Breast cancers in men are often diagnosed at more advanced stages than in women, and as a result, outcomes may be poorer. The authors noted that while mammographic screening has not been shown to reduce breast cancer mortality rates (the reason screening is performed) in men, the detection rate in this high-risk population (4.96 per 1000 examinations) is comparable to the breast cancer detection rate from screening mammography in average risk women. There were no false-positive (“false alarm”) biopsies in this group. The authors acknowledged one of the primary limitations of their study, the relatively small number of patients, and called for larger studies to confirm their findings. They concluded that their study “suggests that screening mammography should be performed in men at increased risk for breast cancer.”

*If you are not able to access the full study and would like a copy, please email me: contact at drattai dot com

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.