Early Response to Neo-adjuvant Chemotherapy in Carcinoma of the Breast Predicts Both Successful Breast-Conserving Surgery and Decreased Risk of Ipsilateral Breast Tumor Recurrence

Abstract

n Abstract: Neo-adjuvant chemotherapy enables us to increase the possibility of breast-conserving surgery for large, bulky tumors. However, several studies have reported that ipsilateral breast tumor recurrences (IBTRs) occur more frequently after neo-adjuvant chemotherapy than originally envisaged. Recently, it was demonstrated that clinical early response after neo-adjuvant chemotherapy predicts pathological complete response. In this study, we assessed the association of clinical early response after neo-adjuvant chemotherapy with successful breast-conserving surgery and IBTR risk. Between 1995 and 2002, 114 patients with T 3.1-6 cm, N 0 or 1, M 0 breast cancer who were candidates for mastectomy but desired breast-conserving surgery were treated with neo-adjuvant chemotherapy. After two cycles of anthracyclinebased neo-adjuvant chemotherapy and before surgery, breast tumors were measured by palpation or ultrasound. Clinical response after two cycles of chemotherapy was defined as positive when the largest tumor dimension was reduced by 30% or greater. Median follow-up time was 72 months. After two cycles of neo-adjuvant chemotherapy, 54 (47.4%) of 114 patients achieved an early response. Patients with the early response underwent breast-conserving surgery significantly more frequently than those without the early response (78% versus 58%, p = 0.03). In addition, the early response was significantly correlated with selection of breast-conserving surgery (odds ratio 3.8, p = 0.01) after adjustments for various clinicopathological factors. Patients without the early response showed significantly lower 6-year IBTR-free survival than patients with the early response (75% versus 97%, p = 0.02). In addition, patients with the early response showed significantly higher 6-year disease-free survival rates than those with the early response (p = 0.02). Multivariate analysis showed that the early response was a predictive factor of IBTR-free survival, being independent of other clinicopathological factors. In conclusion, the early response to neo-adjuvant chemotherapy may be a useful predictor of both selection of surgical method and IBTR risk. n Key Words: breast cancer, early response, ipsilateral breast tumor recurrence, neo-adjuvant chemotherapy N eo-adjuvant chemotherapy is increasingly used in the management of operable breast cancer patients with large tumors with the expectation of breast-conserving surgery. Also, neo-adjuvant chemotherapy increases the possibility of breast-conserving surgery without decreasing the long-term outcome (1). However, recent meta-analysis has reported high local recurrence rates in patients who underwent breastconserving surgery after neo-adjuvant chemotherapy (2). Therefore, it is quite important to identify the predictive factors of breast conservation eligibility and the risk of ipsilateral breast tumor recurrences (IBTR) as early as possible in order to minimize the adverse events of neo-adjuvant chemotherapy for non-responders. However, few data are available concerning whether b...

Breast-conserving surgery in locally advanced breast cancer submitted to neoadjuvant chemotherapy. Safety and effectiveness based on ipsilateral breast tumor recurrence and long-term follow-up

“…Few studies have examined a sufficient number of cases to assess the rates of recurrence in patients subjected to NC and BTC 11,33,34. In the present study, which evaluated a large sample over a long follow-up period, the morphologic response, although valid, was not significantly associated with recurrence, whereas the RECIST-B response was shown to have prognostic value in a multivariate analysis.…”

“…Several factors are associated with IBTR and LRR. Better results were observed in patients who showed an early response to treatment 33 and were positive for hormonal receptors 12; poorer outcomes were reported for patients with lymphovascular invasion11, residual tumors larger than 2 cm 11, multifocal disease after chemotherapy 11,34, no expression of hormonal receptors, stage III and N2-3 axillary nodal status 15, age ≤40 years old, excision margins ≤2 mm, and S-phase fraction >4% 30.…”

PIK3CA-AKT pathway predominantly acts in developing ipsilateral breast tumor recurrence long after breast conserving surgery

“…In 20 years from 1999 to 2018, we surgically treated 2,770 patients with breast cancer, of which 1,881 (68%) underwent breast-conserving therapy (BCT). During the same period, we have experienced only 52 cases of recurrence within the conserved breast (2.3%), which is not a high frequency, as the 10-year IBTR has been reported to be 1-5% [5,6]. However, because of the preservation of breast tissue, it was extremely important to determine whether the recurrence was due to "leftover" or new cancer.…”

“…Improvement of diagnostic modality for the extent of tumor spread and optimal treatment by radiation and adjuvant chemotherapies have obviously contributed to the decrease of LR rate [4]. However, LR still have occurred 1-5% in 10 years [5,6]. In addition, a question still remains whether this ipsilateral breast tumor recurrence (IBTR) is a true recurrence of the residual primary tumor or clonally different new primaries.…”

PIK3CA-AKT pathway predominantly acts in developing ipsilateral breast tumor recurrence long after breast-conserving surgery

“…However, LR still have occurred 1-5% in 10 years [21,32]. In addition, a question still remains whether this ipsilateral breast tumor recurrence (IBTR) is a true recurrence of the residual primary tumor or clonally different new primaries.…”