Sequential anthracyclines (A) plus taxanes represent a standard adjuvant regimen for early TNBC patients. The potential risk for long-term toxicities led to studies exploring the use of A-free options with partly inconsistent results. We here addressed this question by conducting a non-inferiority meta-analysis. We queried Embase, MEDLINE, PubMed, ASCO, and ESMO proceedings to identify randomised clinical trials comparing A-free and A-based regimens. Given the differences in study design, we applied the raw number of events to calculate the risk ratios (RR) for recurrence or death. The non-inferiority (NI) margin was defined as the inverse of the product of the unconfounded treatment effects of A plus taxanes versus A, and A versus no chemotherapy, based on estimates from the EBCTCG 2012 meta-analysis on adjuvant chemotherapy. To improve the specificity, a conservative NI margin was defined using the upper bounds (UB) of the EBCTCG confidence intervals (CI). We retrieved 3,317 potentially eligible records and 8 studies were included in the meta-analysis (4,328 patients in total). The median follow-up time was in the range of 40-97 months. The RR for recurrence with A-free compared to A-based therapy was 1.06, with the UB of the 95% CI (0.93-1.21) falling within the NI margin (1.75). Using the conservative NI margin for recurrence (1.43), A-free regimens still proved non-inferior. A sensitivity analysis excluding trials using CMF as an A-free regimen showed similar results (RR 0.97, 95% CI 0.83-1.12). The RR for death from any cause with A-free compared to A-based therapy was 1.12, with the UB of the 95% CI (0.92-1.36) falling within the NI margin (1.4). A-free regimens did not prove non-inferior to A-based chemotherapy when using the 1.15 conservative NI margin. In the largest meta-analysis to date, A-free regimens proved non-inferior to A-based adjuvant therapy for risk of recurrence. However, non-inferiority could not be shown for risk of death when applying a conservative NI margin. These results may support the adoption of A-free regimens. The observed, substantial study heterogeneity calls for caution when interpreting these findings.

Cancer patients/survivors are at high risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and two- to threefold more likely to develop severe complications and death,1 with female sex being relatively protected.2 Little evidence is currently available about specific associations between coronavirus disease-19 (COVID-19) and breast cancer (BC).

Lenvatinib (Len) was approved by the FDA and EMA as 1st-line treatment for rDTC pts. This study aims to describe the efficacy and toxicity of Len treatment in a monocentric real-life multidisciplinary-based management of rDTC pts.

PT are rare fibroepithelial tumors accounting for < 1% of all breast tumors. We assessed clinicopathological features and their prognostic effect in a single-institution patients cohort. Patients diagnosed with PT between 2001 and 2008 at our Institution were identified. Clinical, surgical and pathological features were collected. Phyllodes-related relapse (PRR) was defined as locoregional or distant recurrence (contralateral excluded). 115 patients with benign, 30 with borderline and 21 with malignant PT were identified. Features associated with malignant PT were: younger age, larger T size, higher mitotic count, marked cytologic atypia, stromal overgrowth, stromal hypercellularity, necrosis and heterologous differentiation (all p<0.01). The majority of malignant PT patients received mastectomy (63.2% vs 3% of benign/borderline, p<0.001) and had negative surgical margins (83.3%). 4-yr cumulative PRR incidence was 7% for benign/borderline and 21.3% for malignant PT (p=0.107). In the entire cohort, marked cellular atypia and heterologous differentiation were associated with worse PRR-free survival (HR 14.10, p=0.036 for marked vs mild atypia; HR 4.21, p=0.031 for heterologous differentiation present vs absent). For patients with benign PT larger tumor size was associated with worse PRR-free survival (HR 9.67, p=0.013 for T>5cm vs T<2cm,). Positive margins were a poor prognostic factor for malignant PT patients (HR 16.61, p=0.025). Overall, 4 patients died because of PT: 3 patients with malignant and 1 with borderline PT. Patients with malignant PT had increased rates of PRR and phyllodes-related death. Cellular atypia and heterologous differentiation were poor prognostic factors in the entire cohort; large tumor size and positive margins were associated with increased risk of PRR in benign and malignant PT, respectively.

Background: Trastuzumab + pertuzumab + taxane and ado-trastuzumab emtansine (T-DM1) are standard first and second-line therapies for HER2+ metastatic breast cancer. Lapatinib is approved in combination with capecitabine in trastuzumab-resistant patients and in combination with letrozole in hormone receptor positive HER2+ pts for whom endocrine treatment is indicated. In Italy, L is also approved in combination with trastuzumab for hormone receptor-negative HER2+ pts. There are only few data on the activity of lapatinib in pts who received prior pertuzumab and /or T-DM1. Methods: We retrospectively analysed HER2+ metastatic breast cancer pts who received lapatinib after prior pertuzumab and/or T-DM1 from July 2013 to June 2018. Objective response rate (ORR) was assessed according to RECIST 1.1. Progression-free survival (PFS) was calculated from lapatinib-based therapy starting to disease progression (PD) or last follow-up. Overall Survival (OS) was calculated from lapatinib-based therapy starting to death or last follow up. Results: Data from 32 HER2+ mBC treated with lapatinib-based therapy were recorded: 30 pts (94%) received lapatinib combined with capecitabine, 1 pt received lapatinib combined with letrozole and 1 pt received lapatinib combined with trastuzumab. All patients had been treated with prior T-DM1 and 9 (28%) with prior pertuzumab for metastatic breast cancer. Setting of treatment with lapatinib-based therapy was: 2° line (n=2, 6%), 3° line (n=17, 53%) and >4° line (n=13, 41%). Patients characteristics were as follows: median age 55 years (range 35-71), hormone receptor positive 66% (n=21), stage IV at diagnosis 34% (n=11), visceral involvement at lapatinib-based therapy starting 91% (n=29). As of June 2018, lapatinib-based therapy was ongoing for 4 pts and 28 pts discontinued treatment due to disease progression (median number of courses for these pts was 8.5, range 2-27). ORR in evaluable pts was: complete response (n=1, 3%), partial response (n=13, 41%), stable disease (n=9, 28%), disease progression (n=9, 28%). Median PFS was 6.4 months (95% CI 3.0-9.8). As of June 2018, 14 pts (44%) were alive, median OS was 11.8 months (95% CI 9.9-13.6). Conclusion: These results confirm that lapatinib-based therapy retains clinical efficacy in HER2+ metastatic breast cancer pts treated with prior pertuzumab and/or T-DM1 and represents a valid therapeutic option in this setting. Citation Format: Frezzini S, Giarratano T, Dieci MV, Giorgi CA, Griguolo G, Vernaci G, Menichetti A, Mantiero M, Tasca G, Faggioni G, Falci C, Miglietta F, Mioranza E, Angelini S, Ghiotto C, Conte P, Guarneri V. Lapatinib-based therapies after pertuzumab and/or T-DM1 for HER2+ metastatic breast cancer patients [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-18-24.

Background The value of adding carboplatin (Cb) to neoadjuvant chemotherapy for TNBC is debated. Current evidence supports the association between Cb use and increased pathological complete response (pCR) rate. However, treatment schedules and doses adopted in randomized trials were not always consistent with those used in clinical practice. Methods Clinicopathological data of TNBC (ER & PgR Results 166 patients were included: 61% treated with AT, 39% with AT+Cb (all patients in this group received Cb AUC2 weekly administered concomitantly to the taxane segment). Main characteristics: median age 50 yrs, ductal histology 93%, grade 3 90%, cT > 2cm 86%, cN + 57%, median TILs 10%, median Ki67 60%, BRCA mutated 10%. After propensity score matching, pCR rate was significantly higher for AT+Cb vs AT: 52% vs 31% (OR 2.39 95%CI 1.04-5.50, p = 0.040). In multivariable analysis, treatment with AT+Cb maintained an independent association with pCR: OR 2.51 95%CI 1.03-6.11, P = 0.043. The achievement of pCR was significantly associated with improved disease-free survival (HR 0.16, 95%CI 0.06-0.45). No difference in DFS was observed comparing AT+Cb vs AT: HR 0.99, 95%CI 0.44-2.25. Conclusions We confirmed in a clinical practice setting the association of Cb-containing neoadjuvant chemotherapy with higher pCR rates. Additional data are needed to clarify the impact on long-term survival. These data support the conditional positive recommendation for Cb inclusion in neoadjuvant chemotherapy for TNBC provided by the Italian Association of Medical Oncology Guidelines on Breast Cancer. Funding Has not received any funding. Disclosure M.V. Dieci: Advisory / Consultancy: Eli Lilly; Advisory / Consultancy: Celgene; Advisory / Consultancy: Genomic Health. V. Guarneri: Advisory / Consultancy: Eli Lilly; Advisory / Consultancy: Novartis; Advisory / Consultancy: Roche; Speaker Bureau / Expert testimony: Eli Lilly; Speaker Bureau / Expert testimony: Novartis; Research grant / Funding (institution): Roche. All other authors have declared no conflicts of interest.

Abstract Background: Brain metastases (BM) are a serious relatively common complication of breast cancer (BC). We evaluated prognostic factors for survival after diagnosis of BM from BC in a contemporary cohort of pts. Methods:Pts diagnosed with BM from BC between 1999 and march 2016 and treated at the Istituto Oncologico Veneto of Padua were evaluated. Overall survival (OS) was defined as time from BM diagnosis to death or last follow-up. Pts were classified in 4 categories according to the breast cancer-specific Graded Prognostic Assessment (GPA) index according to validated criteria (Sperduto et al, 2012), based on age, Karnofsky Performance Status (KPS) and BC phenotype. Cox proportional models were used to calculate HR and 95% CI. Results: 199 pts were identified. Median age at BM diagnosis was 56 yrs (range 28-84). Tumor phenotype distribution was as follows: triple negative (TN, 20.1%), hormone receptor (HR)-HER2+ (16.8%), HR+HER2+ (24.0%) and HR+HER2- (39.1%). Median time to BM diagnosis was 48.9 months (range 0-327), with significant differences according to tumor phenotype (median 27.3, 31.8, 46.1 and 55.2 months in TN, HR-HER2+, HR+HER2+, HR+HER2-, respectively, p=0.009). With respect to OS, no significant difference was observed across tumor phenotypes, with TN patients experiencing the worse outcome (median: 4.7, 7.7, 11.0 and 6.2 months in TN, HR-HER2+, HR+HER2+, HR+HER2-, p=0.187). The breast-specific GPA index, which combines tumor phenotype with patient-related features, was significantly associated with OS (Table). The number of local treatment received (radiotherapy, either whole brain or stereotactic, or neurosurgery) and the administration of systemic treatment after BM diagnosis were significantly associated with better OS (Table). Patients in the less favorable GPA category (GPA index <1) were less likely to receive systemic treatment after BM diagnosis compared to other GPA categories (43% vs 71%, p=0.009); no association between GPA category and local treatment was observed. Patients undergoing increased lines of local treatments where more likely to receive systemic therapy (chi2 square test p<0.001). To avoid bias we performed two separate multivariate analyses including: i) GPA category and number of local treatments; ii) GPA category (patients with GPA index <1 excluded) and systemic treatment. GPA maintained a significant prognostic value in both models (p=0.002 and p=0.038, respectively). Both local and systemic treatments added independent prognostication beyond GPA (Table). Prognostic factorsMedian OS, months (95%CI)HR (95%CI), univariatep, univariateHR (95%CI), corrected for GPAGPA category 3.5-418.8 (15.2-22.5)ref -2.5-38.8 (3.8-13.8)1.40 (0.80-2.43) -1.5-25.5 (3.5-7.5)1.76 (1.00-3.10) -0-1.02.7 (1.2-4.3)2.67 (1.35-5.28)0.019-Number of local tretaments received 03.0 (1.8-7.5)ref ref18.0 (5.8-10.3)0.53 (0.38-0.74) 0.54 (0.38-0.78)221.3 (15.2-27.3)0.36 (0.20-0.65) 0.49 (0.26-0.93)335.5 (33.5-37.6)0.12 (0.04-0.38)<0.0010.08 (0.02-0.33)Systemic treatment yes13.1 (8.7-17.4) no2.6 (1.3-3.8)0.42 (0.30-0.58)<0.0010.46 (0.31-0.68) Conclusions: Patient-related features, tumor phenotype and multimodal treatments all independently contribute to modulate the prognosis of pts with BM from BC. Citation Format: Griguolo G, Dieci MV, Giarratano T, Giorgi CA, Orvieto E, Ghiotto C, Falci C, Mioranza E, Tasca G, Milite N, Miglietta F, Conte P, Guarneri V. Factors related to the prognosis of breast cancer patients after the development of brain metastases [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-12-06.

Chemotherapy-induced alopecia (CIA) affects the majority of patients receiving chemotherapy (CT) for early breast cancer. It is a highly distressing side effect of CT, with psychological and social impact. Primary aim of the present analysis was to assess the efficacy of scalp cooling with DigniCap® in preventing CIA. Success rate was defined as patients' self-reported hair loss <50% according to Dean scale. In this analysis, we reported success rate at 3 weeks after the first CT course and at 3 weeks after the last CT course. Secondary endpoints included self-reported tolerability and patients' judgment on scalp cooling performance. Consecutive early breast cancer patients admitted to Istituto Oncologico Veneto who were recommended to receive neoadjuvant or adjuvant CT, were eligible to undergo scalp cooling during the CT administration within this study. 135 patients were included: 74% received adjuvant CT and 26% neoadjuvant CT (P < .001). The type of CT was: docetaxel-cyclophosphamide (26%), paclitaxel (23%), epirubicin-cyclophosphamide followed by paclitaxel (32%), and paclitaxel followed by epirubicincyclophosphamide (19%). The rate of success in preventing alopecia was 77% (104/135) at 3 weeks from the start of CT and 60% (81/135) at 3 weeks from the end of treatment. Higher success rates were reported in non-anthracycline (71%) compared to anthracycline-containing CT regimens (54%; P < 0.001). Premature discontinuation of scalp cooling was reported in 29/135 patients (21.5%), including withdrawal for alopecia (16/29), for low scalp cooling tolerability (8/29) or both (5/29). Scalp cooling was generally well tolerated. These results overall suggest that the use of scalp cooling is effective in preventing alopecia in the majority of early breast cancer patients receiving neoadjuvant or adjuvant CT, especially for patients undergoing a taxane-based non-anthracycline regimen.

Abstract Background: Tumor infiltrating lymphocytes (TILs) have emerged as a prognostic and potential predictive factor in early triple negative (TN) and HER2+ breast cancer (BC). The prognostic role of TILs in advanced disease is largely unknown. Methods: 109 HER2+ and TNBC patients with available tumor tissue from regional/distant BC recurrence (collected between 2001 and 2015) were identified from a prospectively maintained database at the Istituto Oncologico Veneto of Padova (Italy). Ipsilateral in-breast relapse/second primaries and contralateral BC were excluded from the definition of recurrence. StrTILs were assessed according to consensus guidelines (Salgado, 2014) on hematoxylin and eosin stained slides from BC recurrence samples and, when available, matched primaries. Post-progression survival was calculated as the time from first BC recurrence to last follow up or death. Results: StrTILs were evaluable on recurrent BC for 72 cases (HER2+ n=43, TN n=29), after exclusion of lymphnode metastases. Median time to recurrence from initial BC diagnosis was longer for HER2+ than TN cases: 37 months (95%CI 23-51) and 18 months (95%CI 13-23), respectively. Accordingly, median time to biopsy of recurrence from initial BC diagnosis was 43 months (95%CI 35-51) for HER2+ patients and 20 months (95%CI 9-31) for TN patients. Site of biopsy was visceral metastasis in 54% and soft tissue metastasis in 46% of cases (similar for HER2+ and TN). Median StrTILs level on recurrence was 5% (Q1 2,5%, Q3 10%), without differences according to TN or HER2+ phenotype (Student's t-test p=0.5). In the whole cohort, post-progression survival did not differ for patients with high (>10%) vs low (<10%) StrTILs on recurrence (HR 0.83 95% CI 0.38-1.80, p=0.64). In the TN subgroup, high StrTILs on recurrence were associated to a better post-progression survival (median not reached vs 12.7 months for StrTILs >10% and <10%, respectively, HR 0.03 95%CI 0.00-3.64, log-rank p=0.019). To the opposite, in the HER2+ subgroup, high StrTILs were associated to worse post-progression survival compared to low StrTILs (median 27.7 vs 41.1 months for high vs low StrTILs, HR 2.93 95%CI 1.17-7.31, log-rank p=0.016). Test for interaction between tumor phenotype and StrTILs was p=0.15. Similar results were obtained when including only those patients maintaining a concordant TN or HER2+ phenotype on both primary tumor and recurrence (n=59). StrTILs were assessed on matched primary tumors for 43 patients. Overall, no significant StrTILs variation between primary tumor and recurrence was observed (mean change -4.5%, Wilcoxon p=0.5). Mean change was -2.5% and -7% in HER2+ and TN cases (Wilcoxon p=0.63 and p=0.15, respectively). For TN patients with StrTILs <10% on recurrence, a significant reduction from the primary tumor was observed (mean StrTILs 16% and 4% on primary and recurrent BC, respectively, Wilcoxon p 0.008). Conclusions: Levels of StrTILs on recurrent BC seem to have an opposite effect on prognosis of metastatic BC patients according to tumor phenotype. Immunohistochemical characterization of TILs is ongoing, data will be available for the meeting. Citation Format: Dieci MV, Giaratano T, Miglietta F, Griguolo G, Orvieto E, Falci C, Giorgi CA, Mioranza E, Tasca G, Cappellesso R, Ghiotto C, Conte P, Guarneri V. Tumor infiltrating lymphocytes in recurrent HER2+ and triple negative breast cancer: Prognostic value according to tumor phenotype [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-05-20.

Background: Tumor infiltrating lymphocytes (TILs) have emerged as a prognostic and potential predictive factor in early triple negative (TN) and HER2+ breast cancer (BC). The prognostic role of TILs in advanced disease is largely unknown. Methods: 109 HER2+ and TNBC patients with available tumor tissue from regional/distant BC recurrence (collected between 2001 and 2015) were identified from a prospectively maintained database at the Istituto Oncologico Veneto of Padova (Italy). Ipsilateral in-breast relapse/second primaries and contralateral BC were excluded from the definition of recurrence. StrTILs were assessed according to consensus guidelines (Salgado, 2014) on hematoxylin and eosin stained slides from BC recurrence samples and, when available, matched primaries. Post-progression survival was calculated as the time from first BC recurrence to last follow up or death. Results: StrTILs were evaluable on recurrent BC for 72 cases (HER2+ n=43, TN n=29), after exclusion of lymphnode metastases. Median time to recurrence from initial BC diagnosis was longer for HER2+ than TN cases: 37 months (95%CI 23-51) and 18 months (95%CI 13-23), respectively. Accordingly, median time to biopsy of recurrence from initial BC diagnosis was 43 months (95%CI 35-51) for HER2+ patients and 20 months (95%CI 9-31) for TN patients. Site of biopsy was visceral metastasis in 54% and soft tissue metastasis in 46% of cases (similar for HER2+ and TN). Median StrTILs level on recurrence was 5% (Q1 2,5%, Q3 10%), without differences according to TN or HER2+ phenotype (Student9s t-test p=0.5). In the whole cohort, post-progression survival did not differ for patients with high (u003e10%) vs low ( In the TN subgroup, high StrTILs on recurrence were associated to a better post-progression survival (median not reached vs 12.7 months for StrTILs u003e10% and StrTILs were assessed on matched primary tumors for 43 patients. Overall, no significant StrTILs variation between primary tumor and recurrence was observed (mean change -4.5%, Wilcoxon p=0.5). Mean change was -2.5% and -7% in HER2+ and TN cases (Wilcoxon p=0.63 and p=0.15, respectively). For TN patients with StrTILs Conclusions: Levels of StrTILs on recurrent BC seem to have an opposite effect on prognosis of metastatic BC patients according to tumor phenotype. Immunohistochemical characterization of TILs is ongoing, data will be available for the meeting. Citation Format: Dieci MV, Giaratano T, Miglietta F, Griguolo G, Orvieto E, Falci C, Giorgi CA, Mioranza E, Tasca G, Cappellesso R, Ghiotto C, Conte P, Guarneri V. Tumor infiltrating lymphocytes in recurrent HER2+ and triple negative breast cancer: Prognostic value according to tumor phenotype [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-05-20.