Prophylactic Mastectomy Beneficial in High-Risk Women

ORLANDO—Early prophylactic mastectomy benefits women at high risk of hereditary breast cancer, according to a presentation at the 38th Annual Meeting of the American Society of Clinical Oncology (abstract 1694). The study revealed the presence of high-risk premalignant lesions in the removed breast tissue of more than half of the women undergoing the procedure.

"As a physician, I would want to have as much information as possible to guide my patients at high genetic risk of breast cancer through the difficult decision of whether or not to have a prophylactic mastectomy," said presenter and lead author Nicoline Hoogerbrugge, MD, of University Medical Center Nijmegen, The Netherlands. "But unfortunately, very little is known about the early stages of hereditary breast cancer," including the frequency of atypical hyperplasia and ductal carcinoma in situ (DCIS).

Specimens Examined

This prospective study examined breast specimens from 67 women who underwent prophylactic mastectomy in a tertiary referral center because they were thought to have a greater than 30% lifetime risk of breast cancer. Palpation and mammography before mastectomy did not detect breast lesions in any of the women, nor did MRI in the 50% of women who also had that screening test.

The average age of the women was 39; two thirds (67%) were carriers of a BRCA1 or BRCA2 mutation, 25% had had a prophylactic oophorectomy, and 38% had had previous breast cancer. Only one removed breast from each woman was examined.

The investigators performed radiographic and macroscopic examinations of 5-mm tissue slices from suspicious lesions and from random samples from each quadrant of the breast and the nipple area (a mean of 19 samples per breast). The exams revealed one or more different types of high-risk histopathologic lesions in 57% of the women.

These included atypical lobular hyperplasia in 37%, atypical ductal hyperplasia in 39%, lobular carcinoma in situ in 25%, and DCIS in 15%. One woman had a 4-mm invasive carcinoma.

"These percentages are high," Dr. Hoogerbrugge said. "Although we did not have a proper control group, this is much higher than the data from the literature using the same methods."

Age over 40 years was an independent predictor of high-risk lesions (odds ratio 6.6, P = .01). "Women without high-risk lesions were an average of 6 years younger," Dr. Hoogerbrugge said. Bilateral oophorectomy before prophylactic mastectomy protected against high-risk lesions (odds ratio 0.2, P = .02). Surprisingly, previous history of breast cancer did not affect the presence of high-risk lesions in these women.

The number of women having a BRCA mutation was not higher in the group with high-risk lesions. This surprising result was explained by the fact that all of the women who had had prophylactic oophorectomy also had BRCA mutations, "and oophorectomy may have decreased the risk for these high-risk patients," she said.

Because only six patients had the BRCA2 mutation, the investigators could not determine the relative importance of BRCA1 vs BRCA2.

"We were very concerned about the 10 women who had DCIS that was not found on breast examination 1 day before the preventive mastectomy or on mammography at least 3 months prior to the surgery," Dr. Hoogerbrugge said. Four of these women also underwent MRI, which also did not reveal the DCIS. "These lesions were not small," she said. "They were between 2 mm and 4 mm."

In an interview with ONI, Peter Bult, MD, the pathologist at the Hereditary Cancer Clinic, University Medical Center Nijmegen, who did all of the examinations of the breast specimens in the study, commented: "Patients at risk of hereditary breast cancer, especially carriers of BRCA1 and BRCA2 mutations, have a 60% to 85% risk of getting breast cancer; prophylactic simple mastectomy can prevent this burden for nearly 100% of women."

He pointed out, however, that "this is an operation with many psychological aspects and consequences, including
losing a body part. Results of scientific research are needed to help with the decision if and when to perform a prophylactic simple mastectomy."

Dr. Hoogerbrugge concluded that many women at high risk for hereditary breast cancer develop pathological lesions, especially after age 40. "Not all of these lesions may become invasive cancers, but we can’t tell which ones will be dangerous," she said.