Baseline Factors Trump Response to Therapy in Mastectomy Decisions



VIENNA – The decision to undergo breast-conserving surgery depends on baseline characteristics rather than response to therapy, according to a new analysis of data from a phase III trial comparing neoadjuvant regimens for early HER2-positive breast cancer.

Baseline multicentricity or multifocality of the tumor, receptor status, and the type of surgery planned at diagnosis all were found to influence the decision to undergo breast-conserving surgery (BCS) or mastectomy, investigators reported Sept. 30 at the European Society for Medical Oncology Congress.

"These results call for a clear consensus on the role of breast-conserving surgery in patients responding to neoadjuvant therapy," Dr. Carmen Criscitiello told attendees.

"This will ultimately translate the progress in neoadjuvant therapies into improved breast conservation rates," suggested Dr. Criscitiello of the European Institute of Oncology in Milan.

Puzzled by Low BCS Rates

Neoadjuvant therapy has several possible roles, including testing sensitivity to systemic therapy, downstaging tumors to make them operable, eliminating micrometastases, and increasing breast conservation rates, Dr. Criscitiello explained. It was therefore expected that BCS rates would increase significantly in the Neo ALLTO (Neoadjuvant Lapatinib and/or Trastuzumab Treatment Optimisation) trial.

Half of all patients treated with a dual HER2 blockade of lapatinib (Tykerb) and trastuzumab (Herceptin) in addition to paclitaxel achieved a pathological complete response (pCR) in the Neo ALLTO trial. Yet the majority (58.6%) went on to have a mastectomy rather than BCS.

This puzzled investigators, who saw similar BCS rates in patients treated with other regimens in the study. All told, a pCR was achieved by 51.3% of patients treated with lapatinib, trastuzumab, and paclitaxel; 29.5% of those treated with trastuzumab and paclitaxel; and 24.7% given lapatinib and paclitaxel. Yet the respective rates of BCS were 41.4%, 38.9%, and 42.9%.

To investigate why more women did not opt for BCS, the authors examined data on 429 women who had participated in the trial, excluding 26 who did not undergo breast surgery. The records were examined for baseline characteristics including age, multicentricity/multifocality, planned surgery at diagnosis, physical examination before surgery, imaging before surgery, tumor characteristics, and geographic region.

Women were more likely to have BCS than mastectomy if breast-conserving treatment was already planned, they had a lower (T2 vs. T4) tumor grade, or their nodal (N0 vs. N+) status was lower. Geographic location was also important, with women treated in developed countries more likely to have more conservative treatment than those in developing regions.

Conversely, women were more likely to have a mastectomy than BCS if they had more diffuse disease, were estrogen receptor (ER)-negative, and had residual palpable disease.

"Our study suggests that the decision of surgical treatment post neoadjuvant therapy is mainly based on baseline characteristics," Dr. Criscitiello said. The lower rate of BCS in developing countries could be due to the lack of available radiotherapy, she observed.

Identifying pCR Could Be Hitch

"It is disappointing that we get high remission rates and yet a lot of women still have mastectomy," Dr. Ian Smith, commented after hearing these data.

Dr. Smith, a consultant medical oncologist and head of the Breast Unit at the Royal Marsden NHS Foundation Trust in London, noted that a key problem is identifying whether or not a pCR has occurred.

"The fundamental problem is that the surgeon, same as everybody else, doesn’t know if it is a pCR or not until surgery, and I think we have to look at different approaches to guide us," Dr. Smith suggested.

One approach is the use of molecular markers, such as Ki67. Data from the Royal Marsden have shown that Ki67 measured before and after neoadjuvant chemotherapy might help identify patients who could undergo a more conservative surgical approach.

Dr. Smith suggested: "We should be doing a biopsy again after the first course of neoadjuvant treatment and using molecular markers to predict for us who is going to get a pCR, and if they do they may need minimal surgery or they may need no surgery, but that’s another story."

The Neo ALTTO trial was supported by GlaxoSmithKline, but the company had no involvement in the current analysis. Dr. Criscitiello had no disclosures.

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