NATIONAL HARBOR, MD. – Oophorectomy cut the risk of contralateral breast cancer by almost half in women with a family history of BRCA mutations, according to results of a retrospective study of more than 800 women. The benefit was even greater in women diagnosed with breast cancer before age 50.

“Oophorectomy was the most significant predictor of the development of contralateral breast cancer in this group of women,” investigator Kelly A. Metcalfe, Ph.D., said at a breast cancer symposium sponsored by the American Society of Clinical Oncology.

Removing ovaries reduced the risk of contralateral breast cancer by 47% in the entire cohort (relative risk 0.53, P = .007), she reported. Women younger than age 50 had a 55% reduction (RR 0.45, P = .002), but oophorectomy had no effect on risk of contralateral breast cancer in women 50 and older.

The multicenter cohort study followed women from the date of breast cancer diagnosis until contralateral breast cancer was diagnosed, contralateral mastectomy was performed, death, or date of last follow-up.

Women were included if they were part of a family with known BRCA1 or BRCA2 mutations, had stage I or II breast cancer, were 65 years or younger at the time of diagnosis, were diagnosed in 1975 or later, and had no previous cancer diagnosis. Investigators included living and deceased patients to avoid survivorship bias.

Researchers first performed a pedigree review at participating centers in Canada and the United States to identify eligible patients who had first-degree and second-degree relatives with breast cancer (and their age at diagnosis).

Next, they conducted a medical chart review to assess tumor characteristics (size, nodal status, laterality, grade, and ER/PR status) and treatments (chemotherapy, tamoxifen, surgery, radiotherapy, and oophorectomy). All told, 60% of the women had records of oophorectomy.

Lastly, the investigators determined a patient’s vital status, further treatments, and disease status at follow-up – communicating with the patient or next-of-kin. Deaths were confirmed through medical records.

The researchers reviewed 1,866 cases of breast cancer in 615 families. A total of 846 patients – 79% living – were eligible, gave consent, and had medical charts available for review.

The mean year of birth was 1950, and the mean age at diagnosis was 42 years. The women were followed for an average of 11.5 years. Nearly two-thirds (62%) had BRCA1 mutations, and 88% had undergone genetic testing. Among 177 women who died, breast cancer was the cause of death for 83%.

In the full study cohort, 18% were diagnosed with contralateral breast cancer with a mean time between the two diagnoses of 5.7 years. At 5 years, all women in the cohort had a 13% risk of developing contralateral disease, which rose to 34% at 15 years.

“Age was a very important predictor for these women. Women who were diagnosed with young-onset breast cancer (under the age of 50) had a significantly higher risk of developing contralateral breast cancer within the first 15 years,” said Dr. Metcalfe of the nursing faculty at the University of Toronto. For younger women, the risk was 38% at 15 years, compared with 18% in women 50 and older.

At 15 years post diagnosis, a woman younger than 50 years who had not had an oophorectomy had a roughly 60% risk of developing contralateral breast cancer. The risk was roughly 20% in women 50 years or older with intact ovaries.

Family history also appeared to play an important role. “When we looked at the total number of first-degree relatives diagnosed with breast cancer under the age of 50, we saw increases in risk of contralateral breast cancer,” Dr. Metcalfe said.

Among the whole cohort, the risk of contralateral breast cancer increased by a third with every first-degree relative diagnosed with breast cancer under age 50. “This was particularly evident in BRCA1 carriers and early-onset breast cancer,” said Dr. Metcalfe. Risk was increased by roughly 40% in each of these groups.

For women younger than 50 years at diagnosis who still have intact ovaries, the risk of developing contralateral breast cancer at 15 years was 58%. With the addition of two or more first-degree relatives diagnosed with breast cancer under the age 50, the 15-year risk rose to 68%.

“These are the women that we really need to identify and counsel appropriately, when [they are] considering preventive surgery for the development of contralateral breast cancer,” said Dr. Metcalfe. “We need to think about how these women need to be treated, not only to treat that initial breast cancer but also to prevent contralateral breast cancer.”

The authors reported that they have no relevant financial relationships.

Oophorectomy Halves Risk of Contralateral Breast Cancer with BRCA Mutations