Breast Conservation After Neoadjuvant Chemotherapy Less Common in US Than Elsewhere

By David Douglas

January 15, 2020

NEW YORK (Reuters Health) - Neoadjuvant systemic therapy can facilitate breast conservation in certain women with stage II and III operable breast cancer. But compared to other countries, significantly fewer women in the United States make such a choice.

As Dr. Mehra Golshan told Reuters Health by email, "Chemotherapy prior to surgery in breast cancer allows many women who were only eligible for mastectomy to consider lumpectomy. Despite this, more women in the North America, specifically the United States, choose mastectomy or bilateral mastectomy than women in Europe and Asia even if they are negative for a genetic mutation."

As reported in JAMA Surgery, Dr. Golshan of Brigham and Women's Hospital and Dana-Farber Cancer Institute in Boston and colleagues conducted a secondary analysis of a randomized trial (BrighTNess) involving 634 women in 15 countries in North America, Europe, and Asia.

"This is the largest study to look at women with triple negative breast cancer who had genetic testing done prior to chemotherapy and received optimal therapy prior to surgical decision making," Dr. Golshan said.

Patients were randomized to receive 12 weeks of weekly paclitaxel alone or with the addition of carboplatin and/or veliparib. This was followed by four cycles of doxorubicin hydrochloride and cyclophosphamide.

Breast-conserving therapy (BCT) candidacy was assessed by surgeons using clinical and radiographic criteria before and after neoadjuvant chemo. Complete data were available for 604 participants.

Of 141 patients deemed BCT ineligible at baseline, 75 (53.2%) became eligible. The overall proportion of those who were eligible thus rose from 76.5% to 83.8% after neoadjuvant treatment.

Of these 502 patients, 342 (68.1%) underwent BCT. This included 42 (56.0%) of those who converted to become BCT eligible. Compared with patients in North America, those in Europe and Asia were much more likely to undergo BCT (odds ratio, 2.7).

Many BCT-eligible women underwent mastectomy, including 114 (26.0%) of those with negative test results for a deleterious BRCA mutation. Again there was geographic variation, with North American women more likely to undergo unilateral or bilateral mastectomy. They were also significantly more likely to undergo contralateral prophylactic mastectomy (70.4% versus 20.0%).

Overall, Dr. Golshan said in a statement, the difference is profound, but "Our goal here is not to say whether women should have had a lumpectomy instead. The decision isn't wrong - I've been through cancer treatment myself, and it's a very personal process in decision-making. However, it's important to recognize that based on the same medical information, patients in different countries are making very different decisions. The next question to ask is: why?"

Commenting by email, Dr. John Benson, Consultant Surgeon at Addenbrooke's Hospital Cambridge, UK, told Reuters Health, "This secondary analysis of the BrighTNess trial specifically examines conversion rates and not rates of ipsilateral breast tumor recurrence and does not comment on re-excision of margins in breast conserving surgery (BCS) or rates of completion mastectomy."

"However," he went on to say, "it does provide interesting data on surgical choice and consequences of shared decision-making between patients and their physicians. Amongst patients suitable for BCS at the outset, 70% underwent this surgical procedure whereas just over half of the 75 patients who converted to being eligible for BCS after neoadjuvant chemotherapy actually chose this option. It is unclear whether surgeon preference may have influenced this decision with uncertainty about patterns of tumor shrinkage and perhaps a more cautious approach with excision of the original tumor footprint."

"Nonetheless," he continued, "amongst those patients opting for mastectomy in the United States, more than two-thirds chose bilateral mastectomy, suggesting that patient choice was driving the management plan. Interestingly, rates of contralateral surgery were much lower outside the USA and this might be related to managed healthcare systems that are financially independent of insurance companies and prone to rationalization. Likewise, there was 2.7 fold increased likelihood of BCS in Europe and Asia and this applied to patients with BRCA gene mutations who almost invariably chose bilateral mastectomy in the United States."

Dr. Benson concluded, "Patients with triple negative breast cancer (especially when associated with a gene mutation) will likely have less favorable perceptions about risks of ipsilateral and contralateral recurrence and choose more extensive surgery - whether this be unilateral mastectomy instead of BCS or bilateral mastectomy (with or without reconstruction). As concluded by the authors, these aspects of surgical decision making that seem to eschew BCS demand further investigation."

Dr. Golshan and other authors have relationships with AbbVie Inc whose agent veliparib was employed in the BrighTNess trial.

SOURCE: JAMA Surgery, online January 8, 2020.