New insights into the role of gender in breast cancer development

Breast Cancer Research recently published an article about the importance of studying male breast cancer in BRCA1 and BRCA2 mutation carriers. Here we asked Jonine Figueroa to explain more about the research.

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When we study the causes of cancer, we find there are many factors that contribute to the variations in incidence and type of the disease. One of these factors is gender. Gender certainly plays a major role in the incidence of breast cancers.

Breast cancer is so commonly diagnosed in women that we often forget that it also affects men. Male breast cancer (MBC) numbers aren’t huge – less than 1% of breast cancers occur in men – but men have breast tissue too and about one in 1,000 US men will develop breast cancer.

Studies that aim to identify the causes of breast cancer in both men and women could lead to a better understanding of underlying mechanisms of the disease that apply to everyone.

Susceptibility genes

Having close relatives diagnosed with breast cancer is an important risk factor for breast cancer.

Having close relatives diagnosed with breast cancer is an important risk factor for breast cancer. Mutations in the breast cancer susceptibility genes 1 (BRCA1) and 2 (BRCA2) confer a considerably higher risk of contracting the disease and have been linked to early onset breast cancer in families.

Approximately 10% of MBC is associated with mutations in BRCA2, but many MBCs are diagnosed at much later stages than female breast cancers (FBC).

In order to assess differences in MBC and FBC among carriers of the BRCA2 mutation, the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) undertook a large pooling effort. Over 400 breast cancers in men with BRCA1/2 mutations were studied to see whether tumor characteristics of the male breast cancers differed from those of over 9000 BRCA1/2 female carriers.

Male breast cancer diagnosis

The CIMBA analysis confirmed data from previous work that showed breast cancers in men were diagnosed at higher stages of the disease, which has been thought due to delayed breast cancer detection.

They noted that male breast cancers of BRCA2 mutation carriers were also of a higher grade, which is thought to reflect more aggressive disease.

They noted that MBCs of BRCA2 mutation carriers were also of a higher grade, which is thought to reflect more aggressive disease, and were more likely to be estrogen-receptor positive compared to women.

One of the most interesting findings was that MBCs diagnosed in BRCA2 mutation carriers were more likely to be of a higher grade at younger ages than breast cancers diagnosed in men from the general population. Why having a mutation in BRCA2 would differ in the presentation between MBC and FBC is a mystery.

It is important to know that men diagnosed with breast cancer who are also BRCA2 mutation carriers may display more aggressive forms of breast cancer at younger ages. Prevention awareness campaigns and those providing genetic counseling to high-risk families can emphasize this information, which may result in earlier diagnosis for men when it can be treated more effectively. The authors note that the finding could also affect the management of MBC, since it is possible the men could benefit from adjuvant chemotherapy.

Recent large-pooled analyses of non-genetic risk factors for MBC have shown obesity and higher hormone levels also to be significant risk factors for the disease. Future work that modifies lifestyle or other exposures that increase these risk factors could be another important means of prevention of the disease.

As the technology advances

Today’s genetic technologies are accelerating new discoveries about the molecular pathology of tumors, and in this era of precision medicine those discoveries could soon translate into more targeted treatments.

Today’s genetic technologies are accelerating new discoveries about the molecular pathology of tumors, and in this era of precision medicine those discoveries could soon translate into more targeted treatments.

Future work will include looking at large datasets evaluating the tumor genomes of MBC and FBC. Analyzing tumor profiles by genetic factors such as BRCA1/2 mutation status could provide additional insights.

Risk for MBC and FBC differ in terms of other low-risk susceptibility factors, so it will also be important to assess whether their tumors differ within large consortium. Limited data support differences in molecular pathology between MBC and FBC, so differences by prognosis, such as BRCA2 mutation could also be hypothesized.

Breast cancer is heterogeneous and the scientific evidence show that the risks associated with genetic factors vary by race/ethnicity, tumor pathology subtype and gender. As this recent publication shows, studies of well-defined patient subgroups, may provide new insights into the biological basis of breast cancer development and it’s hoped this can be translated into improved patient outcomes.

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2 Comments

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Oliver Bogler

Thanks for the discussion of this paper and some other recent work on male breast cancer. While it is heartening to see the occasional study of this disease (and I try and review new papers on my blog at malebreastcancerblog.org) the reality is that research on male breast cancer is underfunded – not much has changed since I wrote about it a couple of years ago (http://malebreastcancerblog.org/2013/05/02/where-is-the-1-research-funding-for-the-1-of-breast-cancer-patients-men/). As you say so well here, we won’t know what the differences are until we look.

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Jonine

Thanks Oliver for your kind comments. I think awareness is increasing and having survivors and other advocates bring attention to MBC is an important piece to help increase funding. Keep up the great work on your blog!

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