Outcome of patients with metastatic triple negative breast cancer treated with first-line chemotherapy: a single institution retrospective analysis.

PURPOSE: Metastatic triple negative breast cancer (mTNBC) is associated with poor prognosis and limited treatment options. It is known to be high immunogenic, with a high level of programmed cell death-ligand 1 (PD-L1) expression. PD-L1 expression in TNBC does not have a clear prognostic relevance. In this study, we aimed to assess survival outcomes according to PD-L1 expression in the real world. METHODS: We retrospectively analyzed mTNBC patients treated with first-line chemotherapy at European Institute of Oncology with evaluable PD-L1 expression. Primary endpoints were Progression-Free Survival (PFS) and Overall Survival (OS) according to PD-L1 expression. RESULTS: From January 2000 to December 2018, 190 patients fulfilled the inclusion criteria for final analysis. PD-L1 positive (≥ 1%) subgroup showed a median PFS of 6.8 vs 5.6 months in PD-L1 negative subgroup (PFS-HR 1.25, 95% CI 0.89-1.74, p-value = 0.191), while at data cutoff we had 120 deaths in the PD-L1 < 1% population with a median OS of 22.1 months and 42 deaths in PD-L1 positive patients with a median OS of 20.8 months (OS-HR 1.09, 95% CI 0.76-1.55, p-value = 0.64). No difference in PFS and OS was related to the choice of chemotherapy (p-value for PFS: 0.19, p-value for OS: 0.53). CONCLUSION: No differences in clinical outcome were found according to PD-L1 status or chemotherapy regimen chosen. In "unselected" patients, single agent or combination chemotherapy could be appropriate, although in the immunotherapy era patients with newly diagnosed mTNBC should be routinely tested for PD-L1 status. The variability in PD-L1 expression by metastatic site warrants further investigation.

Economic implications of ACOSOG Z0011 trial application into clinical practice at the European Institute of Oncology.

BACKGROUND AND OBJECTIVES: The American College of Surgeons Oncology Group (ACOSOG) Z0011 trial demonstrated that in clinically node-negative women undergoing breast-conserving therapy (BCT) and found to have metastases to 1 or 2 sentinel nodes, sentinel lymph node biopsy (SLNB) alone resulted in rates of local control, disease-free survival, and overall survival equivalent to those seen after axillary lymph node dissection (ALND), but with significantly lower morbidity. Application of the Z0011 guidelines resulted in fewer ALNDs without affecting locoregional recurrence or survival. Changes in practice inevitably affect health care costs. The current study investigated the actual impact of applying the Z0011 guidelines to eligible patients and determined the costs of care at a single institution. PATIENTS AND METHODS: We compared axillary nodal management and cost data in breast cancer patients who met the Z0011 criteria and were treated with BCT and SLNB. Patients were allocated into two mutually exclusive cohorts based on the date of surgery: pre-Z0011 (June 2013 to December 2015) and post-Z0011 (June 2016 to December 2018). RESULTS: Of 3912 patients, 433 (23%) and 357 (17.6%) patients in the pre- and post-Z0011 era had positive lymph nodes. ALND decreased from 15.3% to 1.57% in the post-Z0011 era. The mean overall cost of SLNB in the pre-Z0011 cohort was €1312 per patient, while that for SLNB with completion ALND was €2613. Intraoperative frozen section (FS) use decreased from 100% to 12%. Omitting the FS decreased mean costs from €247 to €176. The mean total cost in the pre-Z0011 cohort was €1807 per patient, while in the post-Z0011 cohort it was €1498. The application of Z0011 resulted in an overall mean cost savings of €309 for each patient. CONCLUSIONS: Application of the Z0011 criteria to patients undergoing BCT at our institution results in more than half a million Euro cost savings.

Prognosis of selected triple negative apocrine breast cancer patients who did not receive adjuvant chemotherapy.

BACKGROUND: Triple negative breast cancer encompasses several biological entities with different outcomes and is a priority to identify which patients require more treatment to reduce the risk of recurrence and which patients need less treatment. PATIENTS AND METHODS: Among the 210 women with first primary invasive apocrine non metastatic breast cancer operated on between January 1998 and December 2016 at the European Institute Oncology, Milan, we identified 24 patients with a pT1-pT2, node-negative, triple negative subtype and Ki-67 ≤ 20% who did not receive adjuvant chemotherapy (CT). We compared the outcome of this cohort with a similar group of 24 patients with ductal tumors who received adjuvant chemotherapy, matched by pathological stage and biological features and also with a similar group of 12 patients with apocrine tumors who received adjuvant chemotherapy. RESULTS: The median age was 64 and 61 years in the apocrine (w/o CT) and ductal group, respectively. The median value of Ki-67 expression was 12% in the apocrine group (w/o CT) and 16% in the ductal group (p < 0.001). After a median follow-up of 7.5 years, no patients in the apocrine group (w/o CT) experienced a breast cancer related event compared with 4 events in the ductal carcinoma group (Gray test p-value = 0.11). CONCLUSIONS: The outcome of selected apocrine triple negative breast cancer patients who did not received adjuvant chemotherapy is excellent and supports a treatment de-escalation. Multicenter projects focusing on the possibility of avoiding adjuvant chemotherapy in selected subtypes of triple negative breast cancers with favorable outcome are warranted.

Feasibility and surgical impact of Z0011 trial criteria in a single-Institution practice.

The purpose of this study is the evaluation of clinical and surgical impact of the Z0011 trial criteria on the management of breast cancer (BC) patients undergoing breast conservative surgery (BCS) at the European Institute of Oncology (IEO). We studied 1386 patients who underwent BCS and sentinel lymph node biopsy (SLNB) from July 2016 to July 2018. Clinical evaluation, breast ultrasound, mammogram, and cyto/histological examination were performed for all patients at the time of diagnosis. Frozen sections of the sentinel lymph node (SLN) were not performed for any patient. Patients who underwent neo-adjuvant therapy were excluded. To evaluate the results before and after the introduction of Z0011 criteria, a group of 1425 patients with the same characteristics who underwent BCS and SLNB from July 2013 to July 2015 were analyzed. We studied the characteristics of the patients by nodal status, and we observed that T stage, tumor grade, and lymphovascular invasion were statistically related with the highest rate of positive SLN. Of the 1386 patients who underwent surgery after the introduction of the Z011 trial, 1156 patients (83.4%) had negative SLN, 230 patients (16.6%) had positive SLN. Subsequent axillary lymph node dissection (ALND) was performed in only 7 cases (3.0%). Of the 1425 patients operated before the introduction of the Z0011 trial, 216 patients had subsequent ALND (15%). The reduction in the number of ALND performed after the introduction of Z0011 is statistically significant, and this could result in a remarkable reduction of the comorbidities of our patients.

Ipsilateral Breast Tumor Reappearance and Contralateral Breast Cancer after Primary Breast Cancer Treatment: A Comprehensive Retrospective Study of 15,168 Patients.

OBJECTIVE: The aim of this retrospective study was to assess the risk factors for developing ipsilateral breast tumor reappearance (IBTR) and de novo contralateral breast cancer (BC) after primary BC treatment. METHODS: Retrospectively, 15,168 consecutive patients with primary monolateral BC were enrolled in this monocentric study (from June 1994 to December 2006). Clinicopathological features, follow-up, and survival at 15 years were considered for statistical analysis. RESULTS: Significant associations of increased risk for IBTR were verified with metastatic axillary lymph nodes (HR 1.37 [1.15-1.62], p = 0.0004), high tumor grade G2 (HR 1.35 [1.05-1.74], p = 0.02) and G3 (HR 1.35 [1.01-1.79], p = 0.04), luminal B (HR 1.51 [1.25-1.82], p < 0.0001), and HER2-positive (HR1.66 [1.14-2.41], p = 0.008) and triple-negative subtype (HR 1.54 [1.07-2.21], p = 0.02). Older age (HR 1.44 [1.08-1.91], p = 0.01) and positive family history (HR 1.85 [1.47-2.32], p < 0.0001) were risk factors for contralateral BC. Significant protective factors for IBTR were hormonotherapy (HR 0.71 [0.59-0.85], p = 0.0003), chemotherapy (HR 0.72 [0.60-0.87], p = 0.001), and radiotherapy (HR 0.73 [0.61-0.87], p = 0.0005). Hormonotherapy was also confirmed as a protective factor for contralateral second BC (HR 0.43 [0.30-0.60], p < 0.0001). CONCLUSIONS: We classified factors for IBTR and contralateral BC in high- and low-risk groups. In the high-risk group, breast surgery still remains more important than in the low-risk group, which seems to benefit more from adjuvant treatments.

Multiple primary non-breast tumors in breast cancer survivors.

PURPOSE: The aim of this study was to assess the frequency of second primary non-breast cancer after breast cancer diagnosis and treatment, and its correlation with clinicopathological features. METHODS: Data from 21,527 patients with primary breast cancer were collected retrospectively in a single cancer centre; 4.1% of the women developed a second non-breast cancer. The most frequently observed second primary tumor affected the digestive tract (27.8%). The frequency of observed cancers was similar to that expected in the general population, excepting for an excess of melanoma [SIR 1.98 (1.52-2.53)], uterine cancers [SIR 1.44 (1.17-1.74)], ovarian cancers [SIR 1.67 (1.31-2.10)], thyroid tumors [SIR 1.54 (1.23-1.92)], and leukemia [SIR 1.57 (1.11-2.16)]. RESULTS: Clinicopathological breast cancer stratification showed a general increased risk of developing a second cancer in older patients, excluding ovarian cancer. An increased risk of developing ovarian cancer after breast cancer diagnosis was observed, in particular, in triple-negative [HR 3.47 (1.91-6.29)], G3 tumors [HR 2.54 (1.10-5.83)] and in positive breast cancer family history [HR 2.19 (1.22-3.94)]. Breast cancer survivors in hormonal therapy treatment are at higher risk for developing a second thyroid cancer [HR 4.00 (1.46-10.9)]. Conversely, adjuvant chemotherapy offered a protective effect on thyroid cancer risk development [HR 0.46 (0.28-0.76)]. CONCLUSIONS: Older age represents the major risk of developing a second primary non-breast cancer, excluding ovarian cancer. Clinical surveillance is required to prevent ovarian and thyroid cancers, respectively, in patients with positive family history, triple negative, G3 breast cancer and during hormonal therapy treatment in postmenopausal status.