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Treatment Recommendations for High- & Low-Risk Early Breast Cancer

Goodwin, Peter

doi: 10.1097/01.COT.0000381212.84815.7a

BARCELONA—A reassuring message was heard here at the European Breast Cancer Conference from the lead investigator of what was described as the first multi-institutional systematic comparison of breast-conserving therapy versus mastectomy among patients diagnosed with breast cancer who are also BRCA1/2 mutation carriers.

“For those who had breast conservation, chemotherapy was critical in reducing the risk of an in-breast recurrence or new cancer,” reported Lori J. Pierce, MD, Professor of Radiation Oncology at the University of Michigan. “With chemotherapy the risk at 15 years was considerably less than in those who did not receive chemotherapy, approaching the reduced risk seen in those who had mastectomy.”

She told conference attendees that the findings should reassure recently diagnosed women who may find the thought of an immediate mastectomy overwhelming that breast conservation is safe.

And overall, the study found that breast-conservation and mastectomy had equivalent outcomes in terms of systemic recurrence and breast cancer-specific and overall survival in all groups whatever the therapy.

Dr. Pierce said that because there are no randomized comparisons of breast conservation and mastectomy in BRCA1/2 carriers, the 15-year outcome data from her group's 655-patient study conducted by investigators in the US, Israel, Australia, and Spain “can help provide important data to patients trying to decide what will be the best treatment for their hereditary breast cancer.”

The rate of ipsilateral recurrence or new cancer at 15 years in patients who had breast-conservation therapy was 23.5% compared with 5.5% among those who received mastectomy, whereas the rate among patients treated with breast conservation plus adjuvant chemotherapy was 11.9%—not significantly different from the mastectomy group, with a hazard ratio associated with lack of chemotherapy of 5.4.

These data strengthen the view that women face no significant risk if they opt for breast conservation, provided they receive chemotherapy, Dr. Pierce said in an interview.

She explained that because women with breast cancer who are carriers of BRCA 1 and 2 generally fall into two groups (those who find they have the mutation before they have a diagnosis of breast cancer and those who discover it at the time of diagnosis), they may be offered different approaches to the treatment of their breast cancer: “Patients who have had more time to think about the possible diagnosis of breast cancer because they have known for some time that they are BRCA1/2 mutation carriers may be more likely to accept mastectomy.”

On the other hand, women who are confronting both a new diagnosis of breast cancer and knowledge that they are a BRCA1/2 carrier may prefer less breast surgery: “This group is faced at one time with the totality of what to do about the BRCA mutation and their known breast cancer,” Dr. Pierce said.

Because the literature generally reveals more recurrent or new breast events following breast conservation in those who have a mutation compared with those who do not, patients are often recommended to undergo mastectomy. “I think it's important, then, to have more data to look at the likely outcomes following mastectomy and to look at factors that could affect the risk of breast events in those who choose breast conservation,” Dr. Pierce said.

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Not Significantly Altered by Adjuvant RT

The four-country study also found that although the rate of contralateral recurrence in patients with BRCA1/2 mutations was found to exceed 40% in all groups it was not significantly altered by adjuvant radiotherapy.

The take-home message for cancer doctors treating patients with breast-conservation therapy, she said, is that chemotherapy reduced the risk of a second breast event almost five-fold and, since the majority of patients now receive chemotherapy, this will help control breast cancer in the treated breast.”

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Genetics Counselor Key

But she noted that for these patients it is extremely important to work with a genetics counselor to discuss these very personal, complex decisions.

“We also showed in our study that for BRCA-2 carriers hormonal therapy also reduced the risk…. But if a patient is interested in breast conservation, and will be receiving chemotherapy to help reduce the risk of a systemic recurrence, our results demonstrate that chemotherapy will also be beneficial for local control,” Dr. Pierce said.

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Contralateral Prophylactic Mastectomy

Also at the meeting, a 390-patient study from The Netherlands reported by Annette Heemskerk-Gerritsen of Erasmus Medical Centre found that contralateral prophylactic mastectomy brought no benefit in survival among patients with breast cancer despite the reduction in contralateral breast cancer events.

The group collected data from the medical records of women with BRCA1/2 mutations and a history of unilateral breast cancer: 138 of these went on to have risk-reducing mastectomy, and outcomes were compared with the remainder of the patients who did not.

54 patients in the non-risk-reducing-mastectomy group over a period of 2,033 patient-years of observation had metastatic disease compared with 18 patients during 642 patient-years of observation in the risk-reducing-mastectomy group. Overall survival was also similar between the groups, with 56 and 16 deaths in the groups, respectively.

There was no effect at all on distant disease-free survival and there was no significant benefit in overall survival, Ms. Heemskerk-Gerritsen added in an interview. “Obviously it reduces the risk of breast cancer, but we have to advise and inform women that that's it for now and that as yet there is no benefit on survival.”

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Low Risk Breast Cancer

At the same session of the Barcelona conference the conclusion of a study from England was that women considering prophylactic contralateral mastectomy after a diagnosis of breast cancer in which inherited factors are not involved should be encouraged to take time to think.

Ajay Sahu, MS, FRCS, Consultant Breast Surgeon at Frenchay Hospital in Bristol, studied the perception of risk at the time of initial diagnosis among 27 patients age 31 to 65 who had already requested contralateral prophylactic mastectomy after their diagnosis. The study found that all patients overestimated their risk of contralateral breast cancer by factors of between five and 10.

After asking each patient about the reason behind the initial request for mastectomy the operation was then deferred while adjuvant chemotherapy and/or radiotherapy was given, and follow up—at six months by breast care nurses and at 12 months by the surgeon—took place. At the end of this time all of the patients were less anxious about their risk, and only four decided to continue with their plan for prophylactic contralateral mastectomy.

Because 23 out of 27 patients would have had unnecessary surgery if the team had implemented their requests promptly, he and his colleagues strongly recommend that clinicians adopt a policy of recommending a “cooling-off” period for all patients who ask for risk-reducing surgery, he said.

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Hear More!

Lori Pierce, Annette Heemskerk-Gerritsen, and Ajay Sahu further discuss their research in an OT Broadcast News interview with Peter Goodwin, accessible on the Podcast link at, or via iTunes.

© 2010 Lippincott Williams & Wilkins, Inc.
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