Double mastectomy to prevent cancer reduces risk of dying in BRCA1 mutation carriers

March 21, 2018, ECCO-the European CanCer Organisation

Healthy women who carry a breast cancer-causing mutation in the BRCA1 gene, not only reduce their risk of developing the disease but also their chances of dying from it if they have both breasts removed, according to new research presented today (Wednesday) at the 11th European Breast Cancer Conference.

However, the study also found that for women with a mutation in the BRCA2 gene, there was no difference in their chances of dying from the disease whether they opted to have their breasts removed (bilateral risk-reducing mastectomy or BRRM) or chose to have closer instead.

The study of 1696 BRCA1 mutation carriers and 1139 BRCA2 mutation carriers in The Netherlands is the first to prospectively follow healthy women, who opted for either BRRM or surveillance, in order to compare their overall risk of dying from any cause and their risk of dying from .

The women were selected from the national Hereditary Breast and Ovarian Cancer Netherlands (HEBON) database. They were healthy, with no previous history of , and had retained both breasts and ovaries at the time of the DNA diagnosis that detected the BRCA1/2 gene mutations. The women were followed from the time of their DNA diagnosis (the earliest was in January 1995) through to June 2017, or the time of their death or last follow-up appointment. During this time 38% (652) of the BRCA1 carriers and 32% (361) of the BRCA2 mutation carriers underwent BRRM.

After an average follow-up time of approximately nine to 11 years, there were seven cases of cancer and 11 deaths (one due to breast cancer) among the BRCA1 mutations carriers who had BRRM, while there were 269 breast cancer cases and 50 deaths (19 due to breast cancer) in the surveillance group. At the age of 65, overall survival among BRCA1 mutation carriers was 90% in the BRRM group compared to 83% in the surveillance group. At the same age, breast cancer-specific survival was 99.6% in the BRRM group compared to 93% for the surveillance group. In other words, BRCA1 mutation carriers opting for BRRM had a lower risk of dying from breast cancer than BRCA1 mutation carriers under surveillance.

For BRCA2 mutation carriers, after an average follow-up time of approximately nine to ten years, there were no cases of breast cancer and two deaths (none due to breast cancer) in the BRRM group, and 144 breast cancer cases and 32 deaths (seven due to breast cancer) in the surveillance group. However, at the age of 65, while overall survival was 95% for the BRRM group compared to 88% for the surveillance group, breast cancer-specific survival was 100% for the BRRM group compared to 98% for the surveillance group. This means that the risk of dying from breast cancer was low for all BRCA2 mutation carriers, and there was no difference between the BRRM group and the surveillance group.

Dr Annette Heemskerk-Gerritsen, a post-doctoral researcher at the Erasmus University Medical Centre (Rotterdam, The Netherlands), told the conference: "For BRCA1 mutation carriers, bilateral risk-reducing mastectomy not only drastically reduces the risk of developing breast cancer but, as a consequence, also improves breast cancer-specific survival when compared to surveillance. For BRCA2 mutation carriers, however, BRRM seems to lead to similar breast cancer-specific survival as surveillance, despite the reduced ."

She said the difference in the chances of dying from breast cancer between BRCA1 and BRCA2 mutation carriers supports the idea that these two mutations result in different types of tumours.

"We observed that BRCA2-associated breast cancers were diagnosed with more favourable characteristics than BRCA1-associated breast cancers. BRCA2-associated cancers were diagnosed at an older age, better differentiated, and were more likely to have receptors for the hormones oestrogen and progesterone and for the human epidermal growth factor (HER2), suggesting that BRCA2 mutation carriers face a better prognosis at diagnosis than BRCA1 mutation carriers."

The results of the study mean that women with BRCA2 gene mutation can choose between BRRM or surveillance knowing that it makes little difference to whether or not they will die from breast cancer. However, they will still be at increased risk of developing the disease, and the treatment for it can be unpleasant and carries its own risks.

Dr Heemskerk-Gerritsen said: "For those BRCA2 mutation carriers who are struggling with the difficult choice between breast cancer surveillance and BRRM because they wish to keep their breasts, and who are willing to face the risk of developing breast cancer and undergoing essential treatment after diagnosis, it might be a relief to know that ongoing intensive surveillance may be as good as BRRM when it comes to breast cancer-specific survival. Our findings contribute to a more individualised counselling process regarding the difficult choice between BRRM and surveillance based on the type of BRCA mutation."

Co-chair of the conference, Professor Isabel Rubio, director of the breast surgical unit at Clinica Universidad de Navarra, Spain, who was not involved with the research, commented: "Women who carry the BRCA1 or BRCA2 gene face real uncertainty about how to reduce their risk of developing breast cancer and the risk of dying from the disease. A double mastectomy is invasive and can have uncomfortable, sometimes serious, adverse effects afterwards, such as losing sensitivity in the breast and nipple areola area, but would seem to reduce the risk of developing the disease. However, women who opt for surveillance live with the knowledge that the disease could develop and then they will have to go through treatment. These are hard choices and every woman is different. The research by Dr Heemskerk-Gerritsen and colleagues gives these women valuable information about their overall risk of death and of dying from the disease on which to base their decisions. More information is warranted to find out the ages at which women gain the greatest benefit from either mastectomy or surveillance."

Explore further: Breast cancer gene does not boost risk of death: study

More information: Abstract no: 134, "Overall survival and breast cancer-specific survival after bilateral risk-reducing mastectomy in healthy BRCA1 and BRCA2 mutation carriers" Wednesday, Poster session

Related Stories

Breast cancer gene does not boost risk of death: study

January 12, 2018
Young women with the BRCA gene mutation that prompted actress Angelina Jolie's pre-emptive and much-publicised double mastectomy are not more likely to die after a breast cancer diagnosis, scientists said Friday.

Genetic predisposition to breast cancer due to non-brca mutations in ashkenazi Jewish women

July 20, 2017
Genetic mutations in BRCA1 and BRCA2 increase the risk of breast and ovarian cancer in Ashkenazi Jewish women. A new article published by JAMA Oncology examines the likelihood of carrying another cancer-predisposing mutation ...

Oophorectomy associated with decrease in breast cancer death in women with cancer, BRCA1 mutation

April 23, 2015
Removal of the ovaries, a procedure known as an oophorectomy, was associated with a 62 percent reduction in breast cancer death in women diagnosed with breast cancer and carrying a BRCA1 gene mutation, according to an article ...

Early first cancer in BRCA1/2 ups risk in opposite breast

December 30, 2015
(HealthDay)—BRCA1/2 mutation carriers have increased risk of contralateral breast cancer (CBC), with age at first diagnosis a significant predictor of CBC risk, according to a study published online Dec. 23 in the Journal ...

Risk for developing new cancer in other breast increased for survivors with BRCA mutation

December 8, 2011
Breast cancer survivors who carry the BRCA1 or BRCA2 genetic mutation are at high risk for developing contralateral breast cancer — a new primary tumor in the other breast — and certain women within this group of ...

Recommended for you

Pushing closer to a new cancer-fighting strategy

December 11, 2018
A molecular pathway that's frequently mutated in many different forms of cancer becomes active when cells push parts of their membranes outward into bulging protrusions, Johns Hopkins researchers report in a new study. The ...

Scientists have identified and modelled a distinct biology for paediatric AML

December 11, 2018
Scientists have identified and modelled a distinct biology for paediatric acute myeloid leukaemia, one of the major causes of death in children.

HER2 mutations can cause treatment resistance in metastatic ER-positive breast cancer

December 11, 2018
Metastatic breast cancers treated with hormone therapy can become treatment-resistant when they acquire mutations in the human epidermal growth factor receptor 2 (HER2) that were not present in the original tumor, reports ...

Loss of two genes drives a deadly form of colorectal cancer, reveals a potential treatment

December 11, 2018
Colorectal cancers arise from earlier growths, called polyps, found on the inner surface of the colon. Scientists are now learning that polyps use two distinct molecular pathways as they progress to cancer, called the "conventional" ...

Successful anti-PD-1 therapy requires interaction between CD8+ T cells and dendritic cells

December 11, 2018
A team led by a Massachusetts General Hospital (MGH) investigator has found that successful cancer immunotherapy targeting the PD-1 molecule requires interaction between cytotoxic CD8+ T cells, which have been considered ...

Taking uncertainty out of cancer prognosis

December 11, 2018
A cancer diagnosis tells you that you have cancer, but how that cancer will progress is a terrifying uncertainty for most patients. Researchers at Cold Spring Harbor Laboratory (CSHL) have now identified a specific class ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.