Neoadjuvant Systemic Therapy Improves Eligibility for Breast-Conserving Surgery in TNBC

Neoadjuvant systemic therapy may enable patients with triple-negative breast cancer (TNBC) who are ineligible for breast conservation therapy (BCT) to become eligible, according to a prespecified secondary analysis of the results from the phase III BrighTNess trial.

“Surgical results from the BrighTNess trial demonstrate that neoadjuvant chemotherapy makes breast conservation possible in half of patients with stages II to III TNBC who would have otherwise required mastectomy, increasing the overall percentage of those eligible for BCT from 76.5% at diagnosis to 83.8% after [neoadjuvant systemic therapy],” study authors wrote.

The primary end point of the trial was pathological complete response (pCR), and secondary end points included event-free survival, rate of conversion to be eligible for BCT after therapy, and overall survival. BCT eligibility was determined by the patient’s surgeon. The study included 501 patients with clinical stage II disease and 108 patients with clinical stage III disease. In addition, 85 patients were positive for a germlineBRCAmutation.

In patients who were eligible for BCT after neoadjuvant systemic therapy (n = 425), the pCR rate was 55.3%, which was similar between the 165 patients who chose BCT (55.0%) versus the 66 patients who opted for a mastectomy (52.8%;P= .72). However, the pCR rate was not significantly different from the 37 patients who converted to BCT-eligible following the therapy (49.3%; P= .38). The pCR rate was 36.4% in 24 patients out of 66 who were not converted to BCT-eligible following therapy (P= .12) versus 32.3% in the 10 out of 31 patients who converted from BCT-eligible to -ineligible after therapy.

Out of 599 patients assessed for BCT eligibility prior to neoadjuvant systemic therapy, 141 patients (23.5%) were ineligible for BCT on the basis of tumor size in 92 patients (65.2%), tumor location in 33 patients (23.4%), and multicentric disease in 14 patients (9.9%). The reason for ineligibility was unavailable in 2 patients (1.4%). Seventy-five patients (53.2%) were converted to BCT-eligible following neoadjuvant systemic therapy, in which 42 patients (56.0%) went on to receive BCT.

Prior to neoadjuvant systemic therapy, 458 patients were eligible for BCT (76.5%), and 425 patients (92.8%) were still eligible after receiving the therapy. Three-hundred patients (70.6%) underwent BCT following neoadjuvant systemic therapy. In the overall population, the number of patients who were eligible for BCT increased from 458 patients (76.5%) to 502 patients (83.8%) following neoadjuvant systemic therapy, and 342 patients (68.1%) went on to receive BCT.

In the patients who were ineligible for BCT initially (n = 141), specific treatments did not appear to be associated with improved BCT eligibility after neoadjuvant systemic therapy. However, there was a significant difference in progression of patients who were eligible to ineligible across different treatment arms, including 12.8% of patients who received paclitaxel alone, 5.0% of patients who received paclitaxel plus carboplatin, and 4.8% of patients who received the combination plus veliparib (P= .01).

Of the 519 patients with a germlineBRCAmutation, 436 patients (84.0%) were deemed BCT-eligible following neoadjuvant systemic therapy, of which 326 patients (62.9%) underwent BCT. Eighty-three patients (43.0%) of the 193 who underwent mastectomies had bilateral mastectomies.

Among patients who had a deleterious germlineBRCAmutation (n = 85), 68 patients (80.0%) were eligible after neoadjuvant systemic therapy, of which 20 patients (23.5%) underwent BCT. Out of the 65 patients (76.5%) who received mastectomies, 38 patients (58.5%) had a bilateral mastectomy. An additional 114 patients who did not test positive for a germline BRCAmutation underwent mastectomy, which resulted in differences among the regional groups. Four out of 29 patients in North America with a germline BRCAmutation who were eligible for BCT following neoadjuvant systemic therapy underwent mastectomy, and 23 patients (92.0%) underwent bilateral mastectomies. However, 16 of 37 of these patients treated in Europe or Asia underwent BCT, and 8 patients (34.8%) opted for a bilateral mastectomy.

Overall, baseline factors including age, germlineBRCAmutational status, tumor size, smoking history, and region were associated significantly with BCT, whereas patients in Europe and Asia were 2.7-fold more likely to undergo BCT compared with patients in North America (95% CI, 1.84-3..84;&nbsp;P< .001).

BrighTNess is a 3-arm, multicenter, double-blinded, placebo-controlled clinical trial which evaluated patients with operable TNBC of either stages II or III. The trial was conducted across different centers in 15 countries in North America, Europe, and Asia.

Patients whose disease was confirmed by a biopsy were eligible if they had an ECOG performance status of 0 or 1 and had documented BRCA germline mutation testing. If they had received prior anti-cancer treatment for the current breast cancer, had prior treatment with carboplatin, paclitaxel, doxorubicin, cyclophosphamide, and a PARP inhibitor, or received concurrent treatment with an ovarian hormonal replacement therapy or other hormonal agents, they could not be included in the study.

&ldquo;These findings underscore the importance of the breast cancer care team conveying to patients an accurate assessment of their risk of locoregional recurrence, contralateral breast cancer, and second primary cancers, as well as to discuss surgical risks and cosmetic outcomes associated with the various surgical options so that patients can make informed decisions regarding local management,&rdquo; study authors wrote. &ldquo;Surgical oncologists working with breast radiologists also need to incorporate appropriate breast imaging, before and after [neoadjuvant systemic therapy], to improve their assessment of treatment response so that suitable patients can be offered and encouraged to attempt BCT.&rdquo;

Reference:

Golshan M, Loibl S, Wong SM, et al. Breast conservation after neoadjuvant chemotherapy for triple-negative breast cancer: surgical results from the BrighTNess randomized clinical trial [Published Online January 8, 2020].Jama Oncology. doi:10.1001/jamasurg.2019.5410.