RESUMEN
BACKGROUND: Breast cancer (BC) in women aged ≤40 years carrying germline pathogenetic variants (PVs) in BRCA1/2 genes is infrequent but often associated with aggressive features. Human epidermal growth factor receptor 2 (HER2)-low-expressing BC has recently emerged as a novel therapeutic target but has not been characterized in this rare patient subset. METHODS: Women aged ≤40 years with newly diagnosed early-stage HER2-negative BC (HER2-0 and HER2-low) and germline BRCA1/2 PVs from 78 health care centers worldwide were retrospectively included. Chi-square test and Student t-test were used to describe variable distribution between HER2-0 and HER2-low. Associations with HER2-low status were assessed with logistic regression. Kaplan-Meier method and Cox regression analysis were used to assess disease-free survival (DFS) and overall survival. Statistical significance was considered for p ≤ .05. RESULTS: Of 3547 included patients, 32.3% had HER2-low BC, representing 46.3% of hormone receptor-positive and 21.3% of triple-negative (TN) tumors. HER2-low vs. HER2-0 BC were more often of grade 1/2 (p < .001), hormone receptor-positive (p < .001), and node-positive (p = .003). BRCA2 PVs were more often associated with HER2-low than BRCA1 PVs (p < .001). HER2-low versus HER2-0 showed better DFS (hazard ratio [HR], 0.86; 95% CI, 0.76-0.97) in the overall population and more favorable DFS (HR, 0.78; 95% CI, 0.64-0.95) and overall survival (HR, 0.65; 95% CI, 0.46-0.93) in the TN subgroup. Luminal A-like tumors in HER2-low (p = .014) and TN and luminal A-like in HER2-0 (p = .019) showed the worst DFS. CONCLUSIONS: In young patients with HER2-negative BC and germline BRCA1/2 PVs, HER2-low disease was less frequent than expected and more frequently linked to BRCA2 PVs and associated with luminal-like disease. HER2-low status was associated with a modestly improved prognosis.
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Proteína BRCA1 , Proteína BRCA2 , Neoplasias de la Mama , Mutación de Línea Germinal , Receptor ErbB-2 , Humanos , Femenino , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Estudios Retrospectivos , Adulto , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Neoplasias de la Mama/mortalidad , Proteína BRCA1/genética , Proteína BRCA2/genética , Adulto Joven , Supervivencia sin Enfermedad , PronósticoRESUMEN
Importance: The association of tumor-infiltrating lymphocyte (TIL) abundance in breast cancer tissue with cancer recurrence and death in patients with early-stage triple-negative breast cancer (TNBC) who are not treated with adjuvant or neoadjuvant chemotherapy is unclear. Objective: To study the association of TIL abundance in breast cancer tissue with survival among patients with early-stage TNBC who were treated with locoregional therapy but no chemotherapy. Design, Setting, and Participants: Retrospective pooled analysis of individual patient-level data from 13 participating centers in North America (Rochester, Minnesota; Vancouver, British Columbia, Canada), Europe (Paris, Lyon, and Villejuif, France; Amsterdam and Rotterdam, the Netherlands; Milan, Padova, and Genova, Italy; Gothenburg, Sweden), and Asia (Tokyo, Japan; Seoul, Korea), including 1966 participants diagnosed with TNBC between 1979 and 2017 (with follow-up until September 27, 2021) who received treatment with surgery with or without radiotherapy but no adjuvant or neoadjuvant chemotherapy. Exposure: TIL abundance in breast tissue from resected primary tumors. Main Outcomes and Measures: The primary outcome was invasive disease-free survival [iDFS]. Secondary outcomes were recurrence-free survival [RFS], survival free of distant recurrence [distant RFS, DRFS], and overall survival. Associations were assessed using a multivariable Cox model stratified by participating center. Results: This study included 1966 patients with TNBC (median age, 56 years [IQR, 39-71]; 55% had stage I TNBC). The median TIL level was 15% (IQR, 5%-40%). Four-hundred seventeen (21%) had a TIL level of 50% or more (median age, 41 years [IQR, 36-63]), and 1300 (66%) had a TIL level of less than 30% (median age, 59 years [IQR, 41-72]). Five-year DRFS for stage I TNBC was 94% (95% CI, 91%-96%) for patients with a TIL level of 50% or more, compared with 78% (95% CI, 75%-80%) for those with a TIL level of less than 30%; 5-year overall survival was 95% (95% CI, 92%-97%) for patients with a TIL level of 50% or more, compared with 82% (95% CI, 79%-84%) for those with a TIL level of less than 30%. At a median follow-up of 18 years, and after adjusting for age, tumor size, nodal status, histological grade, and receipt of radiotherapy, each 10% higher TIL increment was associated independently with improved iDFS (hazard ratio [HR], 0.92 [0.89-0.94]), RFS (HR, 0.90 [0.87-0.92]), DRFS (HR, 0.87 [0.84-0.90]), and overall survival (0.88 [0.85-0.91]) (likelihood ratio test, P < 10e-6). Conclusions and Relevance: In patients with early-stage TNBC who did not undergo adjuvant or neoadjuvant chemotherapy, breast cancer tissue with a higher abundance of TIL levels was associated with significantly better survival. These results suggest that breast tissue TIL abundance is a prognostic factor for patients with early-stage TNBC.
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Linfocitos Infiltrantes de Tumor , Neoplasias de la Mama Triple Negativas , Adulto , Humanos , Persona de Mediana Edad , Adyuvantes Inmunológicos , Colombia Británica , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/patología , Recurrencia Local de Neoplasia/inmunología , Recurrencia Local de Neoplasia/patología , Estudios Retrospectivos , Neoplasias de la Mama Triple Negativas/inmunología , Neoplasias de la Mama Triple Negativas/mortalidad , Neoplasias de la Mama Triple Negativas/patología , Neoplasias de la Mama Triple Negativas/terapiaRESUMEN
Importance: Young women with breast cancer who have germline pathogenic variants in BRCA1 or BRCA2 face unique challenges regarding fertility. Previous studies demonstrating the feasibility and safety of pregnancy in breast cancer survivors included limited data regarding BRCA carriers. Objective: To investigate cumulative incidence of pregnancy and disease-free survival in young women who are BRCA carriers. Design, Setting, and Participants: International, multicenter, hospital-based, retrospective cohort study conducted at 78 participating centers worldwide. The study included female participants diagnosed with invasive breast cancer at age 40 years or younger between January 2000 and December 2020 carrying germline pathogenic variants in BRCA1 and/or BRCA2. Last delivery was October 7, 2022; last follow-up was February 20, 2023. Exposure: Pregnancy after breast cancer. Main Outcomes and Measures: Primary end points were cumulative incidence of pregnancy after breast cancer and disease-free survival. Secondary end points were breast cancer-specific survival, overall survival, pregnancy, and fetal and obstetric outcomes. Results: Of 4732 BRCA carriers included, 659 had at least 1 pregnancy after breast cancer and 4073 did not. Median age at diagnosis in the overall cohort was 35 years (IQR, 31-38 years). Cumulative incidence of pregnancy at 10 years was 22% (95% CI, 21%-24%), with a median time from breast cancer diagnosis to conception of 3.5 years (IQR, 2.2-5.3 years). Among the 659 patients who had a pregnancy, 45 (6.9%) and 63 (9.7%) had an induced abortion or a miscarriage, respectively. Of the 517 patients (79.7%) with a completed pregnancy, 406 (91.0%) delivered at term (≥37 weeks) and 54 (10.4%) had twins. Among the 470 infants born with known information on pregnancy complications, 4 (0.9%) had documented congenital anomalies. Median follow-up was 7.8 years (IQR, 4.5-12.6 years). No significant difference in disease-free survival was observed between patients with or without a pregnancy after breast cancer (adjusted hazard ratio, 0.99; 95% CI, 0.81-1.20). Patients who had a pregnancy had significantly better breast cancer-specific survival and overall survival. Conclusions and Relevance: In this global study, 1 in 5 young BRCA carriers conceived within 10 years after breast cancer diagnosis. Pregnancy following breast cancer in BRCA carriers was not associated with decreased disease-free survival. Trial Registration: ClinicalTrials.gov Identifier: NCT03673306.
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Neoplasias de la Mama , Genes BRCA1 , Genes BRCA2 , Complicaciones Neoplásicas del Embarazo , Resultado del Embarazo , Adulto , Femenino , Humanos , Embarazo , Neoplasias de la Mama/genética , Neoplasias de la Mama/mortalidad , Supervivencia sin Enfermedad , Mutación de Línea Germinal , Estudios Retrospectivos , Complicaciones Neoplásicas del Embarazo/genética , Complicaciones Neoplásicas del Embarazo/mortalidad , InternacionalidadRESUMEN
Assessment of treatment response in patients (pts) with leptomeningeal metastases (LM) represents a significant challenge and standardized criteria are needed. In 2017, the RANO LM Working Group proposed a standardized scorecard to evaluate MRI findings (further simplified in 2019). Here, we aim to validate the prognostic impact of response to treatment assessed using this tool in a multicentric cohort of breast cancer (BC) pts. Pts with BC-related LM diagnosed at two institutions between 2005 and 2018 were identified. Baseline and follow-up MRI scans were centrally reviewed and response assessment was evaluated using 2019 revised RANO LM criteria. A total of 142 pts with BC-related LM and available baseline brain MRI imaging were identified; 60 of them had at least one follow-up MRI. In this subgroup, median overall survival (OS) was 15.2 months (95%CI 9.5-21.0). At first re-evaluation, radiological response by RANO criteria was: complete response (CR) in 2 pts (3%), partial response (PR) in 12 (20%), stable disease (SD) in 33 (55%) and progression of disease (PD) in 13 (22%). Median OS was 31.1 months (HR 0.10, 95%CI 0.01-0.78) in pts with CR, 16.1 months (HR 0.41, 95%CI 0.17-0.97) in pts with PR, 17.9 months (HR 0.45, 95%CI 0.22-0.91) in pts with SD and 9.5 months in pts with PD (P = .029). A second blinded evaluation showed a moderate interobserver agreement (K = 0.562). Radiological response according to 2019 RANO criteria is significantly associated with OS in pts with BC-related LM, thus supporting the use of this evaluation tool both in trials and clinical practice.
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Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/diagnóstico por imagen , Pronóstico , Imagen por Resonancia Magnética/métodos , Mama , Estudios RetrospectivosRESUMEN
BACKGROUND: Brain metastases (BM) are common among HER2+ breast cancer (BC) and prognostic stratification is crucial for optimal management. BC-GPA score and subsequent refinements (modified-GPA, updated-GPA) recapitulate prognostic factors. Since none of these indexes includes extracranial disease control, we evaluated its prognostic value in HER2+ BCBM. METHODS: Patients diagnosed with HER2+ BCBM at Istituto Oncologico Veneto-Padova (2002-2021) and Montpellier Cancer Institute (2001-2015) were included as exploratory and validation cohorts, respectively. Extracranial disease control at BM diagnosis (no disease/stable disease/response vs. progressive disease) was evaluated. RESULTS: In the exploratory cohort of 113 patients (median OS 12.2 months), extracranial control (n = 65, 57.5%) was significantly associated with better OS at univariate (median OS 17.7 vs. 8.7 months, p = 0.005) and multivariate analysis after adjustment for BC-GPA (HR 0.61, 95% CI 0.39-0.94), modified-GPA (HR 0.64, 95% CI 0.42-0.98) and updated-GPA (HR 0.63, 95% CI 0.41-0.98). The prognostic impact of extracranial disease control (n = 66, 56.4%) was then confirmed in the validation cohort (n = 117) at univariate (median OS 20.2 vs. 9.1 months, p < 0.001) and multivariate analysis adjusting for BC-GPA (HR 0.41, 95% CI 0.27-0.61), modified-GPA (HR 0.44, 95% CI 0.29-0.67) and updated-GPA (HR 0.42, 95% CI 0.28-0.63). CONCLUSIONS: Extracranial disease control provides independent prognostic information in HER2+ BCBM beyond commonly used prognostic scores.
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Neoplasias Encefálicas , Neoplasias de la Mama , Humanos , Femenino , Pronóstico , Neoplasias de la Mama/patología , Neoplasias Encefálicas/secundario , Estudios RetrospectivosRESUMEN
BACKGROUND: The generation of data capturing the risk-benefit ratio of incorporating carboplatin (Cb) to neoadjuvant chemotherapy (NACT) for triple-negative breast cancer (TNBC) in a clinical practice setting is urgently needed. Tumour-infiltrating lymphocytes (TILs) have an established role in TNBC receiving NACT, however, the role of TIL dynamics under NACT exposure in patients receiving the current standard of care is largely uncharted. METHODS: Consecutive TNBC patients receiving anthracycline-taxane [A-T] +/- Cb NACT at three Institutions were enrolled. Stromal-TILs were evaluated on pre-NACT and residual disease (RD) specimens. In the clinical cohort, propensity-score-matching was used to control selection bias. RESULTS: In total, 247 patients were included (A-T = 40.5%, A-TCb = 59.5%). After propensity-score-matching, pCR was significantly higher for A-TCb vs A-T (51.9% vs 34.2%, multivariate: OR = 2.40, P = 0.01). No differences in grade ≥3 haematological toxicities were observed. TILs increased from baseline to RD in the overall population and across A-T/A-TCb subgroups. TIL increase from baseline to RD was positively and independently associated with distant disease-free survival (multivariate: HR = 0.43, P = 0.05). CONCLUSIONS: We confirmed in a clinical practice setting of TNBC patients receiving A-T NACT that the incorporation of weekly Cb significantly improved pCR. In addition, A-T +/- Cb enhanced immune infiltration from baseline to RD. Finally, we reported a positive independent prognostic role of TIL increase after NACT exposure.
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Neoplasias de la Mama Triple Negativas , Humanos , Carboplatino/efectos adversos , Neoplasias de la Mama Triple Negativas/metabolismo , Paclitaxel/efectos adversos , Terapia Neoadyuvante , Antraciclinas/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Linfocitos Infiltrantes de Tumor/metabolismoRESUMEN
INTRODUCTION: Patients with triple-negative breast cancer (TNBC) achieving a pathological complete response (pCR) after neoadjuvant chemotherapy have a better event-free survival. The role of gut microbiome in early TNBC is underexplored. METHODS: Microbiome was analyzed by 16SrRNA sequencing. RESULTS: Twenty-five patients with TNBC treated with neoadjuvant anthracycline/taxane-based chemotherapy were included. Fifty-six percent achieved a pCR. Fecal samples were collected before (t0), at 1 (t1), and 8 weeks (t2) from chemotherapy. Overall, 68/75 samples (90.7%) were suitable for microbiome analysis. At t0, pCR group showed a significantly higher α-diversity as compared with no-pCR, (P = .049). The PERMANOVA test on ß-diversity highlighted a significant difference in terms of BMI (P = 0.039). Among patients with available matched samples at t0 and t1, no significant variation in microbiome composition was reported over time. CONCLUSIONS: Fecal microbiome analysis in early TNBC is feasible and deserves further investigation in order to unravel its complex correlation with immunity and cancer.
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Microbioma Gastrointestinal , Neoplasias de la Mama Triple Negativas , Humanos , Neoplasias de la Mama Triple Negativas/patología , Terapia Neoadyuvante , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Antraciclinas/efectos adversosRESUMEN
INTRODUCTION: The Coronavirus Disease 2019 (COVID-19) has disrupted health services worldwide. The evidence on the impact of the pandemic on cancer care provision, however, is conflicting. We aimed to audit the management of patients diagnosed with early breast cancer (EBC) during the pandemic in a large, tertiary-level cancer center in Italy. METHODS: We conducted a cross-sectional study to track the route to first treatment for patients diagnosed with EBC during 2019, 2020, and 2021. We abstracted data for all consecutive patients referred to the Veneto Institute of Oncology (Padua, Italy). We defined as point of contact (POC) the date of the first consultation with a breast cancer specialist of the breast unit. First treatment was defined as either upfront surgery or neoadjuvant chemotherapy (NACT). RESULTS: We reviewed medical records for 878 patients for whom an MDT report during 2019-2021 (April through June) was available. Of these, 431 (49%) were eligible. The proportion of screen-detected tumors was larger in 2019 and 2021 than in 2020 (59%). Conversely, the proportion of screen-detected tumors was offset by the proportion of palpable tumors in 2020 (Pâ =â .004). Distribution of tumor and nodal stage was unchanged over time, but in situ tumors were slightly fewer in 2020 than in 2019 or 2021. The adjusted odds ratio for treatment delay (45 days or more) was 0.87 for 2020 versus 2019 (95% CI, 0.5-1.53) and 0.9 for 2021 versus 2019 (95% CI, 0.52-1.55). CONCLUSIONS: There was no evidence for major changes in the management of patients with EBC during 2019-2021 and no treatment delays were observed. Our findings suggest that more women presented with palpable nodules at diagnosis, but the stage distribution did not change over time. Validation on a larger cohort of patients is warranted to robustly assess the impact of the COVID-19 pandemic on treatment practices for patients with EBC.
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Neoplasias de la Mama , COVID-19 , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/epidemiología , COVID-19/epidemiología , Estudios Transversales , Pandemias , Italia/epidemiologíaRESUMEN
In patients with human epidermal growth factor receptor 2 positive (HER2+) breast cancer, leptomeningeal metastases (LM) are a rare but often a fatal clinical scenario. In this multicentric study, clinical and pathologic characteristics of patients with HER2+ breast cancer developing LM were described, as well as survival outcomes. Data were gathered retrospectively from medical records of 82 patients with advanced HER2+ breast cancer and LM treated between August 2005 and July 2020. Following LM diagnosis, 79 (96.3%) patients received at least one line of anti-HER2 therapy, 25 (30.5%) patients received intrathecal therapy and 58 (70.7%) patients received radiotherapy. Overall survival (OS) was 8.3 months (95% confidence interval [CI] 5.7-11), 1-year OS was 42%, and 2-year OS was 21%. At univariate analysis, patients who were treated after 2010, had better Karnofsky performance status, were free of neurological symptoms, had better prognostic, received chemotherapy (OS difference 9.4 months, P = .024), or monoclonal antibodies (trastuzumab ± pertuzumab; OS difference 6.1 months; P = .013) after LM diagnosis, had a statistically significantly longer OS. Presence of neurological symptoms (hazard ratio 3.32, 95% CI 1.26-8.73; P = .015) and not having received radiotherapy (hazard ratio 2.02, 95% CI 1.09-3.72; P = .024) were all associated with poorer OS at multivariate analysis. To summarize, not having neurological symptoms and receiving RT at LM diagnosis were associated with prolonged OS in our cohort. Survival seemed to be prolonged with multimodality treatment, which included targeted therapy, chemotherapy, and RT to the LM sites.
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Neoplasias de la Mama , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/metabolismo , Femenino , Humanos , Receptor ErbB-2/metabolismo , Estudios Retrospectivos , Trastuzumab/uso terapéuticoRESUMEN
BACKGROUND: The integration of residual cancer burden (RCB) and post-treatment Ki67 as residual proliferative cancer burden (RPCB) has been proposed as a stronger predictor of long-term outcome in unselected patients with breast cancer (BC) undergoing neoadjuvant chemotherapy (NACT), as compared with RCB. However, no specific analysis in hormone-receptor-positive (HR+) human epidermal growth receptor 2-negative (HER2-) BC is available so far. MATERIALS AND METHODS: A cohort of 130 patients with HR+/HER2- BC who underwent NACT between 2000 and 2014 was included. Archival surgical specimens were evaluated for RCB. RPCB was calculated by combining RCB and Ki67 as previously described. Patients were categorized in four RCB and RPCB categories (pathological complete response and tertiles). Disease-free survival (DFS) and overall survival (OS) estimates were determined by Kaplan-Meier analysis and compared using the log-rank test. Overall change of χ2 and c-indexes were used to compare the performance of the prognostic models. RESULTS: RPCB was calculated for 85 patients. After a median follow up of 8.5 years, RCB was associated with OS (p = .048) but not with DFS (p = .152); RPCB was instead significantly associated with both DFS and OS (p = .034 and p < .001, respectively). In terms of OS, RPCB provided a significant amount of prognostic information beyond RCB (∆χ2 5.73, p < .001). In addition, c-index for OS prediction was significantly higher for RPCB as compared with RCB (0.79 vs. 0.61, p = .03). CONCLUSION: This is the first study evaluating RPCB in patients with HR+/HER2- BC treated with NACT. In this independent cohort, RPCB was a strong predictor of DFS and OS. The better performance of RPCB versus 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 candidates for clinical trials evaluating novel adjuvant strategies. IMPLICATIONS FOR PRACTICE: The present work validated residual proliferative cancer burden (RPCB) as a strong predictor of long-term outcome in patients with hormone receptor-positive human epidermal growth receptor 2-negative (HR+/HER2-) breast cancer (BC) treated with neoadjuvant chemotherapy. In addition, results from the present study suggest RPCB as a promising tool to identify patients with HR+/HER2- BC who might potentially benefit from the inclusion in clinical trials evaluating novel or escalated postneoadjuvant treatment strategies because it allowed to discriminate a subgroup of patients with particularly poor prognosis despite having received subsequent endocrine therapy in the adjuvant setting.
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Neoplasias de la Mama , Neoplasias de la Mama Triple Negativas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Quimioterapia Adyuvante , Femenino , Hormonas , Humanos , Terapia Neoadyuvante , Neoplasia Residual/tratamiento farmacológico , Pronóstico , Receptor ErbB-2/genética , Receptor ErbB-2/uso terapéutico , Neoplasias de la Mama Triple Negativas/tratamiento farmacológicoRESUMEN
Olaparib, an oral PARP-inhibitor, has shown clinical benefit for HER2-negative advanced breast cancer patients carrying a germinal BRCA1/2 mutation. In a randomized Phase III trial, olaparib significantly prolonged progression-free survival as compared with chemotherapy of physician choice. Moreover, in the same trial, a prespecified subgroup analysis reported an overall survival benefit for patients not previously pretreated with chemotherapy for metastatic disease. This review focuses on available preclinical, pharmacokinetic and pharmacodynamic data regarding olaparib and clinical evidence of its antitumor efficacy (both as monotherapy and in combination) and tolerability in breast cancer patients. Open questions, such as use of appropriate biomarkers for patient selection and combination/sequencing with other anticancer drugs, are also addressed.
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Antineoplásicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Ftalazinas/uso terapéutico , Piperazinas/uso terapéutico , Inhibidores de Poli(ADP-Ribosa) Polimerasas/uso terapéutico , Antineoplásicos/farmacología , Neoplasias de la Mama/etiología , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Ensayos Clínicos como Asunto , Reparación del ADN/efectos de los fármacos , Susceptibilidad a Enfermedades , Evaluación Preclínica de Medicamentos , Femenino , Humanos , Metástasis de la Neoplasia , Estadificación de Neoplasias , Ftalazinas/farmacología , Piperazinas/farmacología , Inhibidores de Poli(ADP-Ribosa) Polimerasas/farmacología , Transducción de Señal/efectos de los fármacos , Resultado del TratamientoRESUMEN
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.
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Neoplasias de la Mama , Hipotermia Inducida , Alopecia/inducido químicamente , Alopecia/prevención & control , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/tratamiento farmacológico , Femenino , Humanos , Estudios Prospectivos , Calidad de Vida , Cuero CabelludoRESUMEN
Breast cancer evolves thanks to a dense and close interaction with the surrounding tumor microenvironment (TME). Fibroblasts, leukocytes, blood and lymphatic endothelial cells and extracellular matrix are the constituents of this entity, and they synergistically play a pivotal role in all of the stages of breast cancer development, from its onset to its metastatic spread. Moreover, it has been widely demonstrated that variations to the TME can correspond to prognosis variations. Breast cancer not only modulates the transformation of the environment within the mammary gland, but the same process is observed in metastases as well. In this minireview, we describe the features of TME within the primitive breast cancer, throughout its evolution and spread into the main metastatic sites.
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Antineoplásicos/uso terapéutico , Neoplasias de la Mama/inmunología , Microambiente Tumoral/inmunología , Animales , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Femenino , Humanos , Microambiente Tumoral/efectos de los fármacosRESUMEN
Morphological evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer is gaining momentum as evidence strengthens the clinical relevance of this immunological biomarker. TILs in the post-neoadjuvant residual disease setting are acquiring increasing importance as a stratifying marker in clinical trials, considering the raising interest on immunotherapeutic strategies after neoadjuvant chemotherapy. TILs in ductal carcinoma in situ, with or without invasive carcinoma, represent an emerging area of clinical breast cancer research. The aim of this report is to update pathologists, clinicians and researchers on TIL assessment in both the post-neoadjuvant residual disease and the ductal carcinoma in situ settings. The International Immuno-Oncology Working Group proposes a method for assessing TILs in these settings, based on the previously published International Guidelines on TIL Assessment in Breast Cancer. In this regard, these recommendations represent a consensus guidance for pathologists, aimed to achieve the highest possible consistency among future studies.
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Biomarcadores de Tumor/inmunología , Neoplasias de la Mama/inmunología , Carcinoma in Situ/inmunología , Linfocitos Infiltrantes de Tumor/inmunología , Neoplasia Residual/inmunología , Femenino , Humanos , Oncología Médica/métodos , Terapia Neoadyuvante/métodosRESUMEN
In the light of recent advances in the immunotherapy field for breast cancer (BC) treatment, especially in the triple-negative subtype, the identification of reliable biomarkers capable of improving patient selection is paramount, because only a portion of patients seem to derive benefit from this appealing treatment strategy. In this context, the role of programmed cell death ligand 1 (PD-L1) as a potential prognostic and/or predictive biomarker has been intensively explored, with controversial results. The aim of the present review is to collect available evidence on the biological relevance and clinical utility of PD-L1 expression in BC, with particular emphasis on technical aspects, prognostic implications, and predictive value of this promising biomarker. IMPLICATIONS FOR PRACTICE: In the light of the promising results coming from trials of immune checkpoint inhibitors for breast cancer treatment, the potential predictive and/or prognostic role of programmed cell death ligand 1 (PD-L1) in breast cancer has gained increasing interest. This review provides clinicians with an overview of the available clinical evidence regarding PD-L1 as a biomarker in breast cancer, focusing on both data with a possible direct impact on clinic and methodological pitfalls that need to be addressed in order to optimize PD-L1 implementation as a clinically useful tool for breast cancer management.
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Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Neoplasias de la Mama/patología , Antineoplásicos Inmunológicos/uso terapéutico , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/terapia , Femenino , Humanos , Inmunoterapia , Selección de Paciente , PronósticoRESUMEN
BACKGROUND: The ROXANE Italian prospective study evaluated the impact of the 21-gene Recurrence Score (RS) results on adjuvant treatment decision for patients with early breast cancer. MATERIALS AND METHODS: Nine centers participated. Physicians used the RS test whenever unsure about adjuvant treatment recommendation for patients with estrogen receptor-positive/human epidermal growth receptor 2-negative, T1-T3, N0-N1 early breast cancer. Pre-RS and post-RS treatment recommendations were collected. RESULTS: A total of 251 patients were included. N0 patients (61%) showed higher grade (p < .001) and higher Ki67 (p = .001) and were more frequently progesterone receptor negative (p = .012) as compared with N1 patients. RS results were as follows: <11, n = 63 (25.1%); 11-25, n = 143 (57%); and ≥26, n = 45 (17.9%). Higher RS was found in N0 vs. N1 patients (p = .001) and in cases of G3 (p < .001) and higher Ki67 (p < .001). The rate of change in treatment decision was 30% (n = 75), mostly from chemotherapy (CT) plus hormone therapy (CT + HT) to hormone therapy (HT; 76%, n = 57/75). The proportion of patients recommended to CT + HT was significantly reduced from pre-RS to post-RS (52% to 36%, p < .0001). CT use reduction was more evident for N1 patients (55% to 27%) than for N0 patients (50% to 42%) and was observed only in cases of RS ≤17. CONCLUSION: Physicians predominantly used the 21-gene assay in N0 patients with a more aggressive biology or in N1 patients showing more indolent biology. In this selected patient population, the use of RS testing led to a 30% rate of change in treatment decision. In the N1 patient subgroup, the use of RS testing contributed to reduce CT use by more than half. IMPLICATIONS FOR PRACTICE: This study shows that, even in a context in which physicians recommend a high proportion of patients to endocrine treatment alone before knowing the results of the Recurrence Score (RS) assay, the use of the RS test, whenever uncertainty regarding adjuvant treatment recommendation is present, significantly contributes in further reducing the use of chemotherapy, especially for N1 patients.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/genética , Neoplasias de la Mama/tratamiento farmacológico , Toma de Decisiones Clínicas , Perfilación de la Expresión Génica , Receptor ErbB-2/metabolismo , Receptores de Estrógenos/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Bioensayo , Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/tratamiento farmacológico , Carcinoma Ductal de Mama/genética , Carcinoma Ductal de Mama/patología , Carcinoma Lobular/tratamiento farmacológico , Carcinoma Lobular/genética , Carcinoma Lobular/patología , Quimioterapia Adyuvante , Femenino , Estudios de Seguimiento , Humanos , Italia , Persona de Mediana Edad , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/patología , Pronóstico , Estudios Prospectivos , Receptores de Progesterona/metabolismo , Tasa de SupervivenciaRESUMEN
BACKGROUND: The 8th edition of the American Joint Committee on Cancer (AJCC) staging has introduced prognostic stage based on anatomic stage combined with biologic factors. We aimed to validate the prognostic stage in HER2-positive breast cancer patients enrolled in the ShortHER trial. METHODS: The ShortHER trial randomized 1253 HER2-positive patients to 9 weeks or 1 year of adjuvant trastuzumab combined with chemotherapy. Patients were classified according to the anatomic and the prognostic stage. Distant disease-free survival (DDFS) was calculated from randomization to distant relapse or death. RESULTS: A total of 1244 patients were included. Compared to anatomic stage, the prognostic stage downstaged 41.6% (n = 517) of patients to a more favorable stage category. Five-year DDFS based on anatomic stage was as follows: IA 96.6%, IB 94.1%, IIA 92.4%, IIB 87.3%, IIIA 81.3%, IIIC 70.5% (P < 0.001). Five-year DDFS according to prognostic stage was as follows: IA 95.7%, IB 91.4%, IIA 86.9%, IIB 85.0%, IIIA 77.6%, IIIC 67.7% (P < 0.001). The C index was similar (0.69209 and 0.69249, P = 0.975). Within anatomic stage I, the outcome was similar for patients treated with 9 weeks or 1 year trastuzumab (5-year DDFS 96.2% and 96.6%, P = 0.856). Within prognostic stage I, the outcome was numerically worse for patients treated with 9 weeks trastuzumab (5-year DDFS 93.7% and 96.3%, P = 0.080). CONCLUSIONS: The prognostic stage downstaged 41.6% of patients, while maintaining a similar prognostic performance as the anatomic stage. The prognostic stage is valuable in counseling patients and may serve as reference for a clinical trial design. Our data do not support prognostic stage as guidance to de-escalate treatment. TRIAL REGISTRATION: EUDRACT number: 2007-004326-25; NCI ClinicalTrials.gov number: NCT00629278.
Asunto(s)
Antineoplásicos Inmunológicos/uso terapéutico , Neoplasias de la Mama/diagnóstico , Genes erbB-2 , Estadificación de Neoplasias , Trastuzumab/uso terapéutico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Supervivencia sin Enfermedad , Femenino , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia , PronósticoRESUMEN
PURPOSE OF REVIEW: Current standard for HER2+ early breast cancer patients includes chemotherapy and trastuzumab for 1 year. The purpose of this article is to review available evidence on escalated treatment strategies for high-risk patients and de-escalated treatments for patients at low risk of relapse or high risk of cardiac toxicity. RECENT FINDINGS: Recent results have led to the approval of two adjuvant escalated treatment strategies: pertuzumab and trastuzumab combined with chemotherapy for up to 1 year for high-risk patients; extension of adjuvant anti-HER2 treatment with 1 year of neratinib. However, these treatments are associated with increased costs and toxicity, therefore careful patients' selection is highly required. With regard to de-escalated treatments, the anthracycline-free regimen of adjuvant paclitaxel and 1 year trastuzumab has entered clinical practice for early-stage patients. One year of trastuzumab remains the standard; however, shorter trastuzumab could be an option for low-risk patients and in case of increased risk of cardiotoxocity. Chemotherapy-free regimens are attractive but deserve further evaluation. SUMMARY: There have been advances in treatment individualization for HER2+ early breast cancer patients. Integration of promising biomarkers into risk classification will further help progressing in the field.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/enzimología , Receptor ErbB-2/metabolismo , Anticuerpos Monoclonales Humanizados/administración & dosificación , Antineoplásicos Inmunológicos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/inmunología , Cardiotoxicidad/etiología , Ensayos Clínicos Fase II como Asunto , Ensayos Clínicos Fase III como Asunto , Femenino , Humanos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: Tumor-infiltrating lymphocytes (TILs) evaluated in primary breast cancer (BC) convey prognostic information. Limited data in the metastatic setting are available. METHODS: Secondary lesions from 94 BC patients, 43 triple-negative (TN) and 51 HER2-positive, were evaluated for TILs and expression of CD8, FOXP3, and PD-L1 by immunohistochemistry. RESULTS: TILs levels on metastasis were generally low (median 5%) and did not differ between TN and HER2+ tumors. Younger patients showed significantly lower TILs (p = 0.002). In HER2+ patients, TILs were higher in lung metastases as compared to other sites (p = 0.038). TILs composition was different across metastatic sites: skin metastases presented higher FOXP3 (p = 0.002) and lower CD8/FOXP3 ratio (p = 0.032). Patients treated for metastatic BC prior to biopsy had lower CD8 (overall: p = 0.005, HER2+: p = 0.011, TN: p = 0.075). In TN patients, median overall survival (OS) was 11.8 and 62.9 months for patients with low and high TILs, respectively (HR 0.29, 95%CI 0.11-0.76, log-rank p = 0.008). CD8/FOXP3 ratio was also prognostic in TN patients (median OS 8.0, 13.2, and 54.0 months in 1st, 2nd and 3th tertile, log-rank p = 0.019). Both TILs and CD8/FOXP3 ratio were independent factors at multivariate analysis. Counterintuitively, in HER2+ BC, low TILs tumors showed better prognosis (median OS 53.7 vs 39.9 months in TILs low and TILs high, not statistically significant). CONCLUSIONS: Our findings indicate the relevance of TILs as prognostic biomarker for TNBC even in the advanced setting and provide novel hypothesis-generating data on potential sources of immune heterogeneity of metastatic BC.