Search

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: 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 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) 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.

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 ( 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 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.

Background: The integration of Residual Cancer Burden (RCB) and post-treatment Ki67 (Residual Proliferative Cancer Burden [RPCB] index) has been proposed as a stronger predictor of long-term outcome in unselected breast cancer (BC) patients undergoing neoadjuvant chemotherapy (NACT), as compared to RCB. However, no specific analysis in the subgroup of patients with hormone-receptor (HR)-positive/HER2-negative BC is available so far. We investigated the prognostic value of RPCB in an independent cohort of hormone-receptor (HR) positive/HER2 negative BC patients treated with NACT at our Institution. Methods: A cohort of 130 stage II-III, HR+/HER2 negative BC patients who underwent NACT between 2000 and 2014 was included. Archival surgical specimens were evaluated for RCB (Symmans et al. J Clin Oncol 2007). RPCB was calculated by combining RCB and Ki67 as previously described (Sheri et al, Ann Oncol 2015). Patients were categorized in 4 RCB categories (pathological complete response -pCR- and RCB tertiles) and 4 RPCB categories (pCR and RPCB tertiles). Disease-free Survival (DFS) and overall Survival (OS) estimates were determined by Kaplan-Meier analysis and compared using the log-rank test. The c-index was used to compare the performance of the prognostic models. Results: Patients characteristics were: ductal histology 70%, Grade 3 41%, Stage III 54%, PgR negative (≤10%) 35%, median Ki67 at diagnosis 25%. Neoadjuvant chemotherapy included both anthracycline and taxane in 92% of cases. The rate of pCR was 8%. The vast majority of patients received adjuvant endocrine therapy (96%), whereas 30% received further adjuvant chemotherapy. Median follow up was 8.5 years (95% CI 8.0-9.0). RCB was calculated for 105 patients and RPCB was calculated for 85 patients. RPCB was better than RCB in predicting both DFS and OS (5-year DFS and 8-year OS according to RPCB and RCB are reported in the Table). The c-index for DFS prediction was numerically higher for RPCB vs RCB (0.4042316 vs 0.3396437, p=0.08). Similar results were observed for OS prediction: c-index 0.3099490 (RPCB) vs 0.2372449 (RCB), p=0.08. Conclusions: This is the first study evaluating RPCB specifically in HR+/HER2- BC patients treated with NACT. In this independent cohort, after a median follow up of 8.5 years, RPCB was a strong predictor of DFS and OS. The better performance of RPCB vs RCB was in part due to the ability of RPCB to discriminate a subgroup of patients with a particularly worse prognosis after NACT, who may be candidate for clinical trials evaluating novel adjuvant treatments. Five-year DFS and eight-year OS according to RPCB and RCB5-year DFSp-value8-year OSp-valueRPCBpCR100%0.041100% Citation Format: Federica Miglietta, Vassilena Tsvetkova, Maria Vittoria Dieci, Gaia Griguolo, Grazia Vernaci, Alice Menichetti, Cristina Falci, Giovanni Faggioni, Tommaso Giarratano, Simona Frezzini, Eleonora Mioranza, Marcello Lo Mele, PierFranco Conte, Valentina Guarneri. Validation of residual proliferative cancer burden (RPCB) as a predictor of long-term outcome following neoadjuvant chemotherapy in hormone-receptor positive/HER2 negative breast cancer patients [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-06-12.

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

Background: We evaluated immunohistochemical AR expression and correlation with prognosis in a large series of homogeneously treated patients with primary TNBC.Material and Methods: Patients diagnosed with stage I-III TNBC between 2000 and 2015 at Istituto Oncologico Veneto who received treatment with surgery and neoadjuvant and/or adjuvant chemotherapy were included. Whole tissue slides were stained for AR. AR-positive expression was defined as >1% of positively stained tumor cells. Distant-disease-free survival (DDFS) was calculated from diagnosis to distant relapse or death. Late-DDFS was calculated from the landmark of 3 years after diagnosis until distant relapse or death.Results: We included 263 primary TNBC patients. Mean AR expression was 14% (range 0–100%), and 29.7% (n = 78) of patients were AR+. AR+ vs. AR- cases presented more frequently older age (p < 0.001), non-ductal histology (p < 0.001), G1-G2 (p = 0.003), lower Ki67 (p < 0.001) and lower TILs (p = 0.008). At a median follow up of 81 months, 23.6% of patients experienced a DDFS event: 33.3% of AR+ and 19.5% of AR- patients (p = 0.015). 5 years DDFS rates were 67.2% and 80.6% for AR+ and AR- patients (HR = 1.82 95%CI 1.10–3.02, p = 0.020). AR maintained an independent prognostic role beyond stage, but when TILs were added to the model only stage and TILs were independent prognostic factors. AR was the only factor significantly associated with late-DDFS: 16.4% of AR+ and 3.4% of AR- patients experienced a DDFS after the landmark of 3 years after diagnosis (p = 0.001). Late-DDFS rates at 5 years from the 3-year landmark were 75.8% for AR+ and 95.2% for AR- patients (log-rank p < 0.001; HR = 5.67, 95%CI 1.90–16.94, p = 0.002).Conclusions: AR expression is associated with worse outcome for patients with TNBC. In particular, AR+ TNBC patients are at increased risk of late DDFS events. These results reinforce the rationale of AR targeting in AR+ TNBC.

Background: Neoplastic pericardial effusion (NPE) is a life-threatening condition that can worsen clinical outcome in cancer patients. The optimal management of NPE has yet to be defined because randomized studies are lacking. Objective: We report a retrospective monoinstitutional experience describing characteristics, management and prognostic factors in NPE patients. Design: We reviewed clinical, pathological, and echocardiographic features, therapeutic strategies, and outcome in NPE patients referred to our institute from August 2011 to December 2017. Measurements: Twenty-nine patients with NPE from solid tumors have been identified: 21 lung, 5 breast, and 3 other cancer patients. Results: Median age was 62 years. Most of the patients had Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≥2 (69%) and a symptomatic NPE (69%). In 52% of patients NPE was detected at first diagnosis of metastatic disease, and in 20% of patients pericardium was the only site of metastases. Most of the patients (62%) received systemic therapy, 28% received combined locoregional and systemic therapy, and 10% received locoregional therapy alone. Median overall survival (OS) from NPE diagnosis was 3.9 months. Patients with PS ≥2 had worse OS than patients with better PS

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.

Brain metastases are a serious relatively common complication of breast cancer. We evaluated prognostic factors for survival after diagnosis of brain metastases from breast cancer in a contemporary cohort of patients. Patients diagnosed with breast cancer brain metastases at our institution between 1999 and March 2016 were evaluated. Overall survival was defined as time from brain metastasis diagnosis to death or last follow-up. Patients were classified according to the Breast cancer-specific Graded Prognostic Assessment (BS-GPA), based on age, Karnofsky performance score and breast cancer phenotype. 181 patients were identified. Tumor phenotype distribution was as follows: triple negative (TN, 18.8%), hormone receptor (HR)−HER2+ (16.6%), HR+HER2+ (23.2%) and HR+HER2− (30.9%), not available (10.5%). Median overall survival from brain metastasis diagnosis was 7.7 mos (95% CI 5.4–10.0 mos). Although TN patients experienced the worse outcome, no significant difference was observed across tumor phenotypes (median 5.1, 7.7, 11.0 and 8.6 months in TN, HR−HER2+, HR+HER2+, HR+HER2−, p = 0.081). The BS-GPA index was significantly associated with overall survival (median 18.8, 8.8, 6.2 and 3.6 months, respectively, for BS-GPA categories 3.5–4, 2.5–3, 1.5–2 and 0–1, p = 0.014). Increased number of local treatments for brain metastasis (radiotherapy or neurosurgery) or the administration of systemic therapy after brain metastasis diagnosis were also significant predictors of better overall survival (p