Clinical trial update: implications and management of residual disease after neoadjuvant therapy for breast cancer

Abstract

Neoadjuvant chemotherapy for breast cancer has a well-established role in the management of patients with locally advanced or early stage disease. Multiple trials have demonstrated superior survival outcomes in individuals achieving a pathologic complete response at the time of definitive surgery, and sophisticated genetic methods may predict which patients will be in this category. Those with less than a pathologic complete response remain at significant risk of recurrent disease, and currently no further standard therapy exists. Ongoing studies of novel agents may lead to improved therapeutic outcomes for this high-risk population.Neoadjuvant or preoperative chemotherapy for operable breast cancer treatment was developed to achieve the goals of cytoreduction, with subsequent improvement in the ability to perform breast conservation, treatment of occult micrometastatic disease, and assessment of in vivo sensitivity to a treatment regimen [1]. Multiple trials have demonstrated the benefits and role of treatment with neoadjuvant; however, few studies have evaluated the management of patients after the completion of neoadjuvant therapy, especially those with a suboptimal response.Several large clinical trials have evaluated the role of neoadjuvant chemotherapy for breast cancer. National Surgical Adjuvant Breast and Bowel Project (NSABP) B-18 randomized 1,523 patients with operable breast cancer to receive four cycles of adriamycin and cyclophosphamide (AC) either before or after definitive surgery. In the group treated with neoadjuvant, a rate of pathologic complete response (pCR) in the breast of 13% was observed, with a significantly higher rate of breast conservation (67% versus 60%; P = 0.002) At a median follow-up of 9 years, comparison between the groups treated with neoadjuvant and with adjuvant demonstrated no differences in either disease-free survival (DFS) or overall survival (OS). However, when segregated by pathologic response to treatment with neoadjuvant, individuals achieving a pCR experienced significantly improved outcomes compared with non-pCR subjects, including 9-year DFS (75% versus 58%) and OS (85% versus 73%), and a 50% decrease in the risk of death compared with all other pathologic outcomes (relative risk 0.50, 95% confidence interval 0.32 to 0.78) [2,3]. In a similar study, the European Organization for Research and Treatment of Cancer (EORTC) randomized 698 subjects to anthracycline-based chemotherapy before or after surgery. Again, despite there being no differences in DFS or OS between the neoadjuvant and adjuvant groups, the pCR subgroup, defined as no residual invasive tumor in breast or lymph node tissue, did show improved OS (hazard ratio (HR) 0.86, 95% confidence interval 0.77 to 0.96, P = 0.008) [4]. To investigate the role of exposure to neoadjuvant taxane, the NSABP randomized 2,411 subjects in study B-27 to neoadjuvant AC alone, to neoadjuvant AC and docetaxel before surgery, or to neoadjuvant AC with adjuvant docetaxel after surgery. The addition of the preoperative...

Neoadjuvant chemotherapy for locally advanced breast cancer: a single center experience

“…The NSABP study has shown that ER negative patients had a better response to NAC than ER positive patients [2,12,23]. Similarly in GEPARTRIO study, pCR rates were noted in 41% of triple negative patients, 29% of hormone receptor (HR) negative, and 8% of others [24].…”

“…Neoadjuvant chemotherapy (NAC) is administered with the intention to either convert inoperable locally advanced breast cancer (LABC) to operable state or to downgrade resection from mastectomy to breast sparing surgery [1][2][3]. Because of the tumor size, involvement of regional lymph nodes, extension of the tumor to the chest wall or to the skin; primary resection is difficult in LABC.…”

Staging of Breast Cancer in the Neoadjuvant Setting

“…This may also be possible for patients who have residual disease after completion of neoadjuvant therapy. To this end, a multicenter study has been under way to examine the effects of bevacizumab alone or in combination with other chemotherapies for patients with residual disease after neoadjuvant treatment (29). The expectation that new targeted therapies will soon be available, and that phase I trials are ongoing, demands a mechanism for better determining which patients would be best suited for further therapy (30, 31).…”

Higher expression of EpCAM is associated with poor clinical and pathological responses in breast cancer patients undergoing neoadjuvant chemotherapy

“…Breast cancer is currently one of the most commonly diagnosed neoplasms and is the leading cause of cancer‐related death in women worldwide, accounting for 25 % of cancer diagnoses and 15 % of cancer death per year . Neoadjuvant chemotherapy (NAC) is a standard care regimen that reduces the size of the primary breast tumor to enable breast‐conserving surgery, and decrease the risk of postoperative recurrence, resulting in long‐term survival . The optimal NAC regimen employs a combination of 5‐fluorouracil (5‐FU), epirubicin, and cyclophosphamide (FEC), followed by paclitaxel (PTX) .…”