Search

Purpose of Review: Use of adjuvant chemotherapy significantly reduces the risk of recurrence and improves overall survival (OS) in patients with early-stage breast cancer. However, few data are available on the efficacy of different adjuvant chemotherapy regimens and schedules in patients with hormone receptor positive/HER2-negative (HR+/HER2-) breast cancer. We aim to summarize the available evidence on the efficacy of adjuvant anthracycline-based chemotherapy and of the dose-dense schedule in this specific patient population. Moreover, current controversies in the management of patients with early-stage HR+/HER2- breast cancer are discussed., Recent Findings: Patient-level meta-analysis evaluating the role of the addition of an anthracycline to taxane-based chemotherapy showed that recurrence rate was lower among patients receiving anthracycline-based treatment.Patient-level meta-analysis evaluating the role of different schedules of chemotherapy administration showed that the use of adjuvant dose-dense chemotherapy is associated with significant reduction in breast cancer recurrences and breast cancer mortality. Less evidence is available in the neoadjuvant setting., Summary: For patients with high-risk HR+/HER2- breast cancer, (neo) adjuvant anthracycline and taxane-based chemotherapy, and a dose-dense regimen should still be considered the standard of care. However, in patients with intermediate risk breast cancer candidates to chemotherapy, anthracycline-free regimens could be considered the preferred treatment option., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: We conducted an online survey to investigate oncologists' clinical practices and views on palliative care at the end of life in the Italian region of Liguria., Methods: The survey included 29 items divided into three sections: participant characteristics (n=6), hospital resources and practices (n=11), participant practices and views (n=12)., Results: Twenty-one of the 41 medical oncologists invited completed the survey (51%). Although almost all reported the presence of palliative medicine physicians at their hospitals (90%), nearly half (48%) stated that palliative medicine physicians were not responsible for managing cancer patients at end of life, and 21% reported routine participation of palliative medicine physicians in multidisciplinary meetings. Thirty-eight percent of the respondents stated they never consulted psychologists regarding end of life patient care, and 43% reported they rarely did. Notably, a substantial proportion of participants stated that they administered active treatments to patients with six months life expectancy. Regarding integration between oncology and palliative medicine, an equal proportion felt it had been fully (48%) or partially achieved (48%) at their hospitals., Conclusions: Participants seemed fairly satisfied with the level of integration between oncology and palliative medicine at their hospitals, which contrasts with other findings regarding, for instance, the scant participation of palliative medicine physicians in multidisciplinary meetings. Exploring the impact of the novel regional clinical healthcare pathway for palliative care on practices at hospitals in Liguria will be crucial to ensure that cancer patients at end of life receive quality care., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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., (© 2024 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Introduction: The CLEOPATRA trial (NCT00567190) established a dual anti-HER2 blockade in combination with docetaxel as the first-line standard of care for patients with metastatic HER2-positive breast cancer. While this treatment is overall associated with significant improvement in progression-free survival (PFS) and overall survival (OS), not all patients respond equally. We hypothesized that a radiological complete response (CR) at week 9 (i.e., first disease re-evaluation) is associated with prolonged OS and PFS compared to radiological partial response (PR) or stable disease (SD)., Methods: We performed an exploratory analysis of the CLEOPATRA study to address this question., Results: Out of 362 patients treated with docetaxel, trastuzumab, and pertuzumab eligible for our analysis, 46 (12.7%) had radiological CR at week 9, 243 (67.1%) PR, and 73 (20.2%) SD per central RECIST v1.0. Radiological CR at first tumor re-evaluation was associated with a 60% risk reduction for death compared to SD (adjusted HR = 0.40 95% confidence interval (CI) 0.23-0.70), whereas no significant impact on survival was observed for PR (adjusted HR = 0.85 95% CI 0.60-1.20). The same was observed for PFS with adjusted HR = 0.30 (95% CI 0.18-0.48) for the CR subgroup and adjusted HR = 0.81 (95% CI 0.60-1.09) for the PR subgroup. In multivariate analysis, no variables were associated with radiological CR., Conclusions: Our findings suggest that radiological CR at first disease re-evaluation is associated with more prolonged survival; this might result from stronger dependence on HER2 pathway addiction, supporting the need for further translational research., Competing Interests: Disclosure VD, MB, MC, FJ: none; EA: consultancy fee/honoraria from Eli Lilly, Sandoz, AstraZeneca. Research grant to my Institution from Gilead; Support to attend medical conferences (travel/accommodation/expenses) from Novartis, Roche, Eli Lilly, Genetic, IstitutoGentili, Daiichi Sankyo (all outside the submitted work); CM: honoraria from Novartis and Lilly; DMB: declares full-time employment from the European Society for Medical Oncology since September 1, 2023; speaker's engagement from AstraZeneca, Daiichi Sankyo; meeting/travel grant from Novartis; institutional research funding from Eli Lilly, F. Hoffmann-La Roche Ltd, Novartis; non-remunerated activity as a member of the board of directors for Associaҫão de Investigaҫão e Cuidados de Suporte em Oncologia; non-remunerated leadership role as prior Portuguese Young Oncologists; Committee Chair of Sociedade Portuguesa de Oncologia; GNM: support to attend medical conferences: Roche and Bayer (all outside the submitted work); ML: honoraria and/or advisory board from Roche, Novartis, Lilly, Pfizer, AstraZeneca, Daiichi Sankyo, Gilead, Seagen, MSD, Exact Sciences, Takeda, Ipsen, Sandoz, Libbsand Knight, a travel grant from Gilead and research support (to the Institution) from Gilead (all outside the submitted work); EdA: honoraria and/or advisory board from Roche/GNE, Novartis, Seattle Genetics, Zodiac, Libbsand Pierre Fabre. Travel grants from Roche/GNE and GSK/Novartis. Research grant to his institution from Roche/GNE, Astra-Zeneca, GSK/Novartis, and Servier(all outside the submitted work)., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: To better understand the type of care offered to Italian patients with advanced breast cancer at the End-of-Life (EoL), we conducted a retrospective observational study. EoL was defined as the period of six months before death., Methods: One hundred and twenty-one patients with advanced breast cancer (ABC) treated at IRCCS San Martino Policlinic Hospital who died between 2017 and 2021 were included. Data about patient, disease, and treatment characteristics from breast cancer diagnosis to death, along with information about comorbidities, medications, imaging, specialist evaluations, hospitalization, palliative care and home care, hospice admissions, and site of death were collected., Results: 98.3% of the patients received at least one line of active treatment at EoL; 52.8% were hospitalized during the selected period. Palliative (13.9%), psychological (7.4%), and nutritional evaluations (8.2%) were underutilized. Palliative home care was provided to 52% of the patients. Most of the patients died at home (66.1%) and fewer than one out of five (18.2%) died at the hospital. Among the patients who died at home, 27.3% had no palliative support., Conclusions: Our findings indicate that palliative care in EoL breast cancer patients is still inadequate. Only a minority of patients had psychological and nutritional support While low nutritional support may be explained by the fact that typical symptoms of ABC do not involve the gastrointestinal tract, the lack of psychological support suggests that significant barriers still exist. Data on the site of death are encouraging, indicating that EoL management is increasingly home centered in Italy., (© 2024. The Author(s).)

Opinion Statement: Around 90% of breast tumours are diagnosed in the early stage, with approximately 70% being hormone receptor-positive. The cornerstone of adjuvant therapy for early-stage hormone receptor-positive breast cancer is endocrine therapy, tailored according to disease stage, biological characteristics of the tumour, patient's comorbidities, preferences and age. In premenopausal patients with hormone receptor-positive breast cancer, ovarian function suppression is a key component of the adjuvant endocrine treatment in combination with an aromatase inhibitor or tamoxifen. Moreover, it can be used during chemotherapy as a standard strategy for ovarian function preservation in all breast cancer subtypes. In the metastatic setting, ovarian function suppression should be used in all premenopausal patients with hormone receptor-positive breast cancer to achieve a post-menopausal status. Despite its efficacy, ovarian function suppression may lead to several side effects that can have a major negative impact on patients' quality of life if not properly managed (e.g. hot flashes, depression, cognitive impairment, osteoporosis, sexual dysfunction, weight gain). A deep knowledge of the side effects of ovarian function suppression is necessary for clinicians. A correct counselling in this regard and proactive management should be considered a fundamental part of survivorship care to improve treatment adherence and patients' quality of life., (© 2024. The Author(s).)

Inflammatory breast cancer (IBC) is a rare (1%-5%), aggressive form of breast cancer, accounting for approximately 10% of breast cancer mortality. In the localized setting, standard of care is neoadjuvant chemotherapy (NACT) ± anti-HER2 therapy, followed by surgery. Here we investigated associations between clinicopathologic variables, stromal tumor-infiltrating lymphocytes (sTIL), and pathologic complete response (pCR), and the prognostic value of pCR. We included 494 localized patients with IBC treated with NACT from October 1996 to October 2021 in eight European hospitals. Standard clinicopathologic variables were collected and central pathologic review was performed, including sTIL. Associations were assessed using Firth logistic regression models. Cox regressions were used to evaluate the role of pCR and residual cancer burden (RCB) on disease-free survival (DFS), distant recurrence-free survival (DRFS), and overall survival (OS). Distribution according to receptor status was as follows: 26.4% estrogen receptor negative (ER-)/HER2-; 22.0% ER-/HER2+; 37.4% ER+/HER2-, and 14.1% ER+/HER2+. Overall pCR rate was 26.3%, being highest in the HER2+ groups (45.9% for ER-/HER2+ and 42.9% for ER+/HER2+). sTILs were low (median: 5.3%), being highest in the ER-/HER2- group (median: 10%). High tumor grade, ER negativity, HER2 positivity, higher sTILs, and taxane-based NACT were significantly associated with pCR. pCR was associated with improved DFS, DRFS, and OS in multivariable analyses. RCB score in patients not achieving pCR was independently associated with survival. In conclusion, sTILs were low in IBC, but were predictive of pCR. Both pCR and RCB have an independent prognostic role in IBC treated with NACT., Significance: IBC is a rare, but very aggressive type of breast cancer. The prognostic role of pCR after systemic therapy and the predictive value of sTILs for pCR are well established in the general breast cancer population; however, only limited information is available in IBC. We assembled the largest retrospective IBC series so far and demonstrated that sTIL is predictive of pCR. We emphasize that reaching pCR remains of utmost importance in IBC., (© 2024 The Authors; Published by the American Association for Cancer Research.)

Introduction: In randomized clinical trials (RCTs), blinded independent central review (BICR) is used to minimize heterogeneity and bias associated with radiological response evaluation by local investigators. However, BICR adds costs and complexity to the trial management. We assessed the discrepancy index between progression-free survival (PFS) assessment by local investigators and by BICR in RCTs conducted in patients with metastatic breast cancer (MBC)., Methods: A systematic search of PubMed, Embase, Cochrane databases and conference proceedings (ASCO, SABCS, ESMO) was performed up to January 4, 2023 (PROSPERO: CRD42021229865). All RCTs published from 2000 to 2022, including MBC patients treated in first- or second-line, and reporting PFS assessed by local investigators and BICR were included. A discrepancy index between BICR-assessed and investigator-assessed HR was calculated for each trial and an overall combined DI was obtained using a fixed-effects model. The agreement between hazard ratios (HR) of PFS assessed by local investigators and BICR was measured using intraclass correlation coefficient (ICC)., Results: We analyzed 24 studies including 13,168 patients. Among them, 19 (79%) were in first-line, 18 (75%) were phase III trials and 23 (96%) had PFS as primary endpoint. The overall combined discrepancy index was 0.97 (95%CI 0.85-1.10; ICC 0.831, p < 0.001) suggesting no statistically significant difference in PFS assessment between local investigators and BICR. This result was consistent across all analyzed subgroups., Conclusions: The good concordance between local investigator and BICR assessments supports the reliability of local investigator-assessed PFS as primary endpoint for RCTs in MBC and questions the practical utility of implementing BICR in all RCTs., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Neoadjuvant treatment discriminates responders, but pathologic complete response is uncommon in oestrogen receptor (ER)-positive/HER2-negative early breast cancer. We aimed to assess the prognostic value of Ki-67 index after neoadjuvant endocrine therapy (NET)., Methods: We conducted a systematic literature search of PubMed, Embase, CENTRAL, and conference proceedings up to 22nd August 2023 to identify studies reporting the association of Ki-67 index after NET with recurrence-free survival (RFS) and/or overall survival (OS) in women with ER-positive/HER2-negative early breast cancer. We combined RFS and OS hazard ratios (HRs) with 95% confidence intervals (CIs)., Results: Twelve studies including 7897 patients were analysed. Most studies were clinical trials (n = 7547) including only postmenopausal women (n = 3953) treated with aromatase inhibitor (n = 3359). Three studies evaluated Ki-67 in a preplanned core biopsy at 2-4 weeks of NET (n = 3348), while nine evaluated Ki-67 in the surgical specimen (n = 4549) after 2-24 weeks of NET. Median follow-up ranged between 37 and 95 months for RFS and 62-84 months for OS. High Ki-67 index after NET was significantly associated with worse RFS (HR 2.48, 95% CI 1.86-3.30) and OS (HR 2.66, 95% CI 1.65-4.28). A sensitivity analysis including three studies that measured Ki-67 in a preplanned core biopsy showed similar association with RFS (HR 2.41, 95% CI 1.77-3.30)., Conclusions: High Ki-67 after NET is associated with worse survival outcomes, even after a short course of NET, emphasising the prognostic value of this biomarker in women with ER-positive/HER2-negative early breast cancer., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. Diogo Martins-Branco: Honoraria and advisory board fees from Daiichi Sankyo, Janssen, Pfizer, Merck Sharp & Dohme, Angelini, AstraZeneca, and Novartis, meeting/travel grants from LEO Farmacêuticos, Merck Sharp & Dohme, Ipsen, Janssen, Roche, Laboratórios Vitória, and Novartis, and institutional research grants from F. Hoffmann-La Roche Ltd and Novartis (all outside the submitted work); Guilherme Nader-Marta: Support to attend medical conferences: Roche, AstraZeneca, and Bayer (all outside the submitted work); Chiara Molinelli: Honoraria and advisory board fees from Lilly and Novartis; travel grant by Gilead (all outside the submitted work); Michail Ignatiadis: Honoraria from Novartis, Seattle Genetics; travel grants from Amgen, Roche, Gilead; research grant to my institution Roche/GNE, Pfizer, Natera Inc, Inivata Inc (all outside the submitted work); Philippe Aftimos: Honoraria and advisory board fees from Eli Lilly, Gilead, Menarini, Novartis, and Roche; travel grant from Daiichi Sankyo; and research funding from Roche (all outside the submitted work); Roberto Salgado: Honoraria from BMS, Exact Sciences, and Roche; intellectual property rights/patent from Merk; and research funding from Roche, Merk, and Puma Biotechnology (all outside the submitted work); Evandro de Azambuja: Honoraria and/or advisory board from Roche/GNE, Novartis, SeaGen, Zodiac, Libbs; Pierre Fabre, Lilly, Astra-Zeneca, MSD, and Gilead. Travel grants from Roche/GNE and Astra-Zeneca. Research grant to my institution from Roche/GNE, Astra-Zeneca, GSK/Novartis, and Servier (all outside the submitted work). Lieveke Ameye and Marianne Paesmans have no conflicts of interest to declare., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Up to 20% of breast cancer overexpress HER2 protein, making it a reliable target for antibody-based treatments. In early HER2-positive breast cancer avoiding anthracycline-based chemotherapy is a challenge. Based on the single-arm phase II APT trial results, adjuvant paclitaxel/trastuzumab is an accepted regimen for patients with stage I HER2-positive disease. In our retrospective study of 240 patients, the median tumor size was 12.0 mm (IQR 9 -15), and 204 (85%) had estrogen receptor-positive disease. After a median follow-up of 4.6 years, 3-year real-world disease-free survival, distant DFS, and overall survival were 98.8% (95% confidence interval (CI), 96.2-99.6), 99.2% (95% CI, 96.7-99.8), and 98.3% (95% CI, 96.2-99.6), respectively. In a real-world setting, an adjuvant paclitaxel/trastuzumab regimen was associated with low recurrence rates among women with stage I, HER2-positive breast cancer. Additionally, we reviewed other treatment optimization strategies attempted or ongoing in HER2-positive breast cancer., Competing Interests: Declaration of Competing Interest VD, MS, FJ, MM, MP, IS, WH: none. GNM: Travel grants for meetings from Roche and Bayer, outside the submitted work. EA: Speaking fee/consultancy: Eli Lilly, Sandoz, AstraZeneca. Support to attend medical conferences from Eli Lilly, Roche, Novartis, Genetics, Istituto Gentili, Daiichi Sankyo (all outside the present work). CM: receive fees from Novartis and Lilly outside the submitted work.Ugo De Giorgi received honoraria for advisory boards or speaker fees for Pfizer, BMS, MSD, PharmaMar, Astellas, Bayer, Ipsen, Roche, Novartis, Clovis, GSK, AstraZeneca, Institutional research grants from AstraZeneca, Sanofi and Roche all outside the submitted work. UDG: Advisory boards: Astellas, Bayer, BMS, Ipsen, MSD, Novartis, Pfizer, PharmaMar, Roche; Institutional research grant: AstraZeneca, Roche, Sanofi. AS: Advisory Board: BMS (BRISTOL-MYERS-SQUIBB), Servier,Gilead, Pfizer, Eisai, Bayer, MSD (MERCK SHARP & DOHME); Consultancy: Arqule, Sanofi, Incyte; Speaker’s Bureau: Takeda, BMS, Roche, Abbvie, Amgen, Celgene, Servier, Gilead, Astrazeneca, Pfizer, Arqule, Lilly, Sandoz, Eisai, Novartis, Bayer, MSD. DT: advisory board: Agendia, AstraZeneca, Daiichi Sankyo, Eli Lilly, Medscape, MSD, Novartis, Roche; Travel: AstraZeneca,Pfizer, Roche. FPD: Advisory Board: Amgen, AstraZeneca, Daiichi Sankyo, Gilead Sceince, Lilly, Novartis, Pfizer, Pierre Fabre, Roche, Seagen; Contracted Research: Fondation belge contre le cancer; Institutional grant: AstraZeneca. AB: Advisory board: Argen, BMS, Eli-Lilly, MSD, Novartis, Pfizer, Roche. GB: Advisory board: BMS, Eli Lilly, MSD, Novartis, Pfizer, Roche; Travel: BMS, Eli Lilly, MSD, Novartis, Pfizer, Roche. ML: reports advisory role for Roche, Lilly, Novartis, Astrazeneca, Pfizer, Seagen, Gilead, MSD and Exact Sciences; speaker honoraria from Roche, Lilly, Novartis, Pfizer, Sandoz, Libbs, Daiichi Sankyo and Takeda; Travel Grants from Gilead; Research funding (to the Institution) from Gilead outside the submitted work. EdA: Honoraria and/or advisory board from Roche/GNE, Novartis, SeaGen, Zodiac, Libbs, Pierre Fabre, Lilly, Astra-Zeneca; travel grants from Roche/GNE and Astra-Zeneca; Research grant to my institution from Roche/GNE, AstraZeneca, and GSK/Novartis. MP: Board Member (Scientific Board): Oncolytics; Consultant (honoraria): AstraZeneca, Camel-IDS/Precirix, Gilead, Immunomedics, Lilly, Menarini, MSD, Novartis, Pfizer, Roche-Genentech, Seattle Genetics, Immutep, Seagen, NBE Therapeutics, Frame Therapeutics; Research grants to my Institute: AstraZeneca, Immunomedics, Lilly, Menarini, MSD, Novartis, Pfizer, Radius, Roche-Genentech, Servier, Synthon., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The human epidermal growth factor receptor 2 (HER2)-enriched intrinsic subtype represents up to 75% of all HER2-positive hormone receptor (HR)-negative breast cancer (BC). Optimizing HER2-targeting therapy in this population might allow the omission of anthracycline-based chemotherapy, which is associated with potentially severe toxicities. DECRESCENDO (NCT04675827) is a large, multicenter, single-arm phase II trial in patients with HR-negative, HER2-positive, node-negative early BC evaluating a neoadjuvant pertuzumab and trastuzumab fixed-dose combination administered subcutaneously plus taxane-based chemotherapy followed by adjuvant treatment, adapted according to response to neoadjuvant therapy. The primary end point is the 3-year recurrence-free survival rate in patients with 'HER2-enriched' tumors and a pathological complete response. This flexible care substudy offers adjuvant treatment administration outside the hospital to some patients.

Antibody-drug conjugates (ADCs) are a class of antineoplastic agents whose structure is composed of three main components: a monoclonal antibody (mAB) targeting a specific target antigen, a cytotoxic payload, and a linker binding the antibody to the payload. By combining the specificity of mABs with the high potency of the payloads, ADCs constitute a smart drug delivery system with improved therapeutic index. After recognition and binding of the mAB to its target surface antigen, ADCs are internalized by endocytosis by the tumor cell, releasing the payloads into the cytoplasm, where they exert their cytotoxic activity, eventually leading to cell death. The composition of some of the new ADCs confers additional functional properties that allow expanding their activity to neighboring cells not expressing the target antigen, constituting a valuable strategy to overcome tumor heterogeneity. Some of these 'off-target effects', such as the bystander effect, are possibly the mechanism underlying the antitumor activity demonstrated in patients with low expression of the target antigens, which represents an important paradigm shift in anticancer targeted therapy. Three ADCs are currently approved for the treatment of breast cancer (BC); two anti-HER2 (human epidermal growth factor receptor 2) ADCs (trastuzumab emtansine and trastuzumab deruxtecan); and one Trop-2-targeted ADC (sacituzumab govitecan). Based on the unprecedented efficacy data demonstrated by these agents, ADCs have been incorporated as part of standard regimens for all subtypes of advanced BC, as well as for high-risk early HER2-positive BC. Despite the remarkable advances, several hurdles still remain to overcome, including the development of reliable biomarkers for patient selection, prevention, and management of potentially severe toxicities, ADC resistance mechanisms, post-ADC resistance patterns, and optimal treatment sequencing and combinations. In this review, we will summarize the currently available evidence related to the use of these agents, as well as explore the current landscape of ADC development for BC treatment., (© The Author(s), 2023.)

Objective: Neoadjuvant chemotherapy has become the preferred treatment in HER2-positive early breast cancer. Several trials investigated the neoadjuvant efficacy of dual HER2 blockade with anthracycline-free chemotherapy, whereas few data are available on single-agent trastuzumab and anthracycline-based regimens, which represent the standard of care in the adjuvant setting. This phase II, single-arm trial assessed anthracycline-based chemotherapy and trastuzumab as neoadjuvant treatment for high-risk HER2-positive breast cancer., Methods: Forty-three patients with stage II-III HER2-positive breast cancer were treated with 4 courses of neoadjuvant 5-fluorouracil 600 mg/m 2 , epirubicin 90 mg/m 2 , cyclophosphamide 600 mg/m 2 (FEC ×4) every 21 days, followed by 12 courses of weekly paclitaxel 80 mg/m 2 and trastuzumab 2 mg/Kg IV (loading dose 4 mg/kg)., Results: Pathologic complete response (pCR) was observed in 22 (51%) of 43 patients. After a median follow-up of 6 years, the 5-year disease-free survival and overall survival were 85.8% (95% confidence interval 75.9%-97%) and 89.6% (80.4%-99.8%), respectively. A temporary decrease in left ventricular ejection fraction was observed in two patients. No cardiac death or congestive heart failure occurred. One patient died due to febrile neutropenia., Conclusions: FEC ×4 followed by paclitaxel and trastuzumab was associated with high pCR rates and favorable long-term outcomes. However, this regimen was associated with relevant hematologic toxicity.

Background: Breast cancer is traditionally classified into three clinical subtypes based on hormone receptor and HER2 status (i.e., luminal-like, HER2-positive, and triple negative). Each subtype has distinct clinical-pathological and molecular characteristics and requires tailored treatments. Recent research efforts have been focusing on a new classification, identifying the so-called "HER2-low" category, including tumors characterized by a low level of HER2 expression (immunohistochemistry score 1+ or 2+ without in situ hybridization amplification). Emerging evidence shows that patients with HER2-low tumors can derive benefit from selected anti-HER2 therapies. This represents a major advancement in the field of breast oncology, where a broader proportion of patients with breast cancer can ultimately benefit from new effective targeted treatment strategies., Summary: The antibody-drug conjugate trastuzumab deruxtecan has proven impressive efficacy in patients with HER2-low breast cancer, and several other drugs are currently under investigation in this subset of patients. Additional investigation is needed to address open issues that exist in this field, including appropriate pathological assessment of HER2-low status, clarification of its prognostic implications, and global access to newly approved drugs., Key Message: Our review aims to summarize the available evidence regarding HER2-low breast cancer, illustrating the current challenges that are being addressed and the future perspectives in this exciting new field., Competing Interests: Dr. Molinelli received honoraria from Novartis and Lilly outside the submitted work. Dr. Jacobs declares no conflicts of interest. Dr. Agostinetto received consultancy fees or honoraria from Eli Lilly and Sandoz and support to attend medical conferences from Roche, Novartis, Eli Lilly, and Genetic, Istituto Gentili (all disclosures are outside the submitted work). Dr. Marchiò received honoraria from Bayer, Roche, AstraZeneca, and Daiichi Sankyo. Dr. De Azambuja received honoraria and/or participated to advisory board from Roche/GNE, Novartis, Seattle Genetics, Zodiac, Libbs, and Pierre Fabre; received travel grants from Roche/GNE and GSK/Novartis; and received research grant to his institution from Roche/GNE, AstraZeneca, GSK/Novartis, and Servier. Dr. Schettini received personal fees from Novartis for educational material. Dr. Lambertini played an advisory role for Roche, Lilly, Novartis, Astrazeneca, Pfizer, Seagen, Gilead, MSD, and Exact Sciences and received speaker honoraria from Roche, Daiichi Sankyo, Lilly, Novartis, Pfizer, Sandoz, Libbs, and Takeda and travel grants from Gilead outside the submitted work., (Copyright © 2022 by S. Karger AG, Basel.)

Breast cancer is one of the major causes of cancer-related morbidity and mortality in women worldwide. During the past three decades, several improvements in the adjuvant treatment of hormone receptor-positive/HER2-negative breast cancer have been achieved with the introduction of optimized adjuvant chemotherapy and endocrine treatment. However, estimating the risk of relapse of breast cancer on an individual basis is still challenging. The IRIDE (hIGh Risk DEfinition in breast cancer) working group was established with the aim of reviewing evidence from the literature to synthesize the current relevant features that predict hormone-positive/HER2-negative early breast cancer relapse. A panel of experts in breast cancer was involved in identifying clinical, pathological, morphological, and genetic factors. A RAND consensus method was used to define the relevance of each risk factor. Among the 21 features included, 12 were considered relevant risk factors for relapse. For each of these, we provided a consensus statement and relevant comments on the supporting scientific evidence. This work may guide clinicians in the practical management of hormone-positive/HER2-negative early breast cancers.