Characterization of HER2-low breast cancer in young women with germline BRCA1/2 pathogenetic variants: Results of a large international retrospective cohort study.

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.

Ovarian Suppression: Early Menopause and Late Effects.

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.

The Impact of Initial Tumor Response on Survival Outcomes of Patients With HER2-Positive Advanced Breast Cancer Treated With Docetaxel, Trastuzumab, and Pertuzumab: An Exploratory Analysis of the CLEOPATRA Trial.

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.

Progression-free survival assessment by local investigators versus blinded independent central review in randomized clinical trials in metastatic breast cancer: A systematic review and meta-analysis.

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.

Treatment Response, Tumor Infiltrating Lymphocytes and Clinical Outcomes in Inflammatory Breast Cancer-Treated with Neoadjuvant Systemic Therapy.

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.

Ki-67 index after neoadjuvant endocrine therapy as a prognostic biomarker in patients with ER-positive/HER2-negative early breast cancer: a systematic review and meta-analysis.

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.

DECRESCENDO: de-escalating chemotherapy in HER2-positive, estrogen receptor-negative, node-negative early breast cancer.

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.

Breast cancer is the most frequent cancer type among women worldwide. Different types of breast cancer exist, defined by the type of proteins on the tumor cell surface: HER2-positive: overproduction of human epidermal growth factor receptor 2 (HER2); Hormone receptor-positive: overproduction of the estrogen and/or progesterone hormone receptors. In the past 30 years, effective anti-HER2 drugs have been developed. However, they are often combined with chemotherapy, which can cause serious side effects (also called toxicities). HER2-positive tumors, which are also hormone receptor-negative, respond better to HER2-targeting drugs with less toxicity than chemotherapy. The DECRESCENDO trial aims to test treating HER2-positive, hormone receptor-negative patients (with a maximum breast cancer tumor size of 5 cm, without swollen lymph nodes) with pertuzumab + trastuzumab. The combination therapy would be given presurgery to reduce the tumor size as much as possible first (known as neoadjuvant therapy). The intensity of the patient's chemotherapy would be reduced with only one chemotherapy drug instead of standard three to four drugs. Patients that respond well will require less intense treatment after their surgery. Tissue from the tumors will be tested to see if any of the HER2-positive tumors belong to a subtype known as 'HER2-enriched' ­ this subtype is predicted to be more responsive to the trastuzumab and pertuzumab combination therapy. In a separate study of the DECRESCENDO trial, patients with good responses to neoadjuvant therapy and no safety concerns may continue their postsurgery treatment outside the hospital, such as at home.

Real-world clinical outcomes of patients with stage I HER2-positive breast cancer treated with adjuvant paclitaxel and trastuzumab.

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.

Antibody-drug conjugates: the evolving field of targeted chemotherapy for breast cancer treatment.

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.

Anthracycline, taxane, and trastuzumab-based neoadjuvant chemotherapy in HER2-positive early breast cancer: phase II trial.

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/m2, epirubicin 90 mg/m2, cyclophosphamide 600 mg/m2 (FEC ×4) every 21 days, followed by 12 courses of weekly paclitaxel 80 mg/m2 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.

Definition of High-Risk Early Hormone-Positive HER2-Negative Breast Cancer: A Consensus Review.

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.

HER2-Low Breast Cancer: Where Are We?

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.

Impact of Baseline and On-Treatment Glycemia on Everolimus-Exemestane Efficacy in Patients with Hormone Receptor-Positive Advanced Breast Cancer (EVERMET).

PURPOSE: The mTOR complex C1 (mTORC1) inhibitor everolimus in combination with the aromatase inhibitor exemestane is an effective treatment for patients with hormone receptor-positive (HR+), HER2-negative (HER2-), advanced breast cancer (HR+/HER2- aBC). However, everolimus can cause hyperglycemia and hyperinsulinemia, which could reactivate the PI3K/protein kinase B (AKT)/mTORC1 pathway and induce tumor resistance to everolimus. EXPERIMENTAL DESIGN: We conducted a multicenter, retrospective, Italian study to investigate the impact of baseline and on-treatment (i.e., during first 3 months of therapy) blood glucose levels on progression-free survival (PFS) in patients with HR+/HER2- aBC treated with everolimus-exemestane. RESULTS: We evaluated 809 patients with HR+/HER2- aBC treated with everolimus-exemestane as any line of therapy for advanced disease. When evaluated as dichotomous variables, baseline and on-treatment glycemia were not significantly associated with PFS. However, when blood glucose concentration was evaluated as a continuous variable, a multivariable model accounting for clinically relevant patient- and tumor-related variables revealed that both baseline and on-treatment glycemia are associated with PFS, and this association is largely attributable to their interaction. In particular, patients who are normoglycemic at baseline and experience on-treatment diabetes have lower PFS compared with patients who are already hyperglycemic at baseline and experience diabetes during everolimus-exemestane therapy (median PFS, 6.34 vs. 10.32 months; HR, 1.76; 95% confidence interval, 1.15-2.69; P = 0.008). CONCLUSIONS: The impact of on-treatment glycemia on the efficacy of everolimus-exemestane therapy in patients with HR+/HER2- aBC depends on baseline glycemia. This study lays the foundations for investigating novel therapeutic approaches to target the glucose/insulin axis in combination with PI3K/AKT/mTORC1 inhibitors in patients with HR+/HER2- aBC.

Trastuzumab emtansine (T-DM1) as adjuvant treatment of HER2-positive early breast cancer: safety and efficacy.

Introduction: The prognosis of patients with HER2-positive early breast cancer has radically improved after the introduction of (neo)adjuvant anti-HER2 targeted therapy. Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate combining the anticancer properties of the anti-HER2 agent trastuzumab and the antineoplastic cytotoxic drug DM1. After demonstrating to be an effective and safe treatment for patients with HER2-positive advanced breast cancer, the development of T-DM1 has moved to the early setting.Areas covered: The aim of this review is to explore the current role of T-DM1 in the treatment landscape of HER2-positive early breast cancer, focusing specifically on the efficacy and safety data available in the adjuvant setting.Expert opinion: T-DM1 is an effective and safe treatment option in the adjuvant setting for patients with HER2-positive breast cancer without pathologic complete response after standard neoadjuvant chemotherapy plus anti-HER2 targeted therapy. With the availability of more effective anti-HER2 targeted agents, including T-DM1, there is an urgent need for more chemotherapy de-escalation research efforts in the early setting.

Update on the Management of Breast Cancer during Pregnancy.

The diagnosis of breast cancer during pregnancy represents a challenging situation for the patient, her caregivers and physicians. Pregnancy adds complexity to oncological treatment planning, as many therapies can be potentially dangerous to the fetus. Therefore, a multidisciplinary approach is needed to offer a proper care for obtaining the best possible outcomes for the mother and the future child. Breast surgery is feasible throughout the pregnancy while radiotherapy should be postponed after delivery. Administration of chemotherapy is considered safe and can be given during the second and third trimesters, while it is contraindicated in the first trimester due to the high risk of fetal malformations. Endocrine therapy and targeted agents are not recommended during the whole pregnancy period; however, limited data are available on the use of the majority of new anticancer drugs in this context. The aim of the current review is to provide an update on the current state of art about the management of women diagnosed with breast cancer during pregnancy.

Dose-dense adjuvant chemotherapy in early breast cancer patients: 15-year results of the Phase 3 Mammella InterGruppo (MIG)-1 study.

BACKGROUND: Adjuvant chemotherapy is the standard of care in high-risk early breast cancer patients. Dose-dense should be the preferred schedule of administration. However, its long-term benefit is unknown. METHODS: In the Italian multicentre Phase 3 randomised MIG-1 trial, node-positive and high-risk node- negative breast cancer patients were randomised to receive six cycles of adjuvant fluorouracil, epirubicin and cyclophosphamide regimen administered every 3 (FEC21) or 2 (FEC14) weeks. The primary endpoint was overall survival (OS), and the secondary endpoint was event-free survival (EFS). RESULTS: From 1992 to 1997, 1214 patients were included. Median follow-up was 15.8 years. In all, 15-year OS was 71% and 68% in the FEC14 and FEC21 groups, respectively (HR = 0.89; p = 0.25). In all, 15-year EFS was 47% and 43% in the FEC14 and FEC21 groups, respectively (HR = 0.87; p = 0.18). In a pre-planned subgroup analysis, among patients with hormone receptor-negative tumours, 15-year OS was 70% and 65% in the FEC14 and FEC21 groups, respectively (HR = 0.73; 95% CI: 0.51-1.06); 15-year EFS was 58% and 43% in the FEC14 and FEC21 groups, respectively (HR = 0.70; 95% CI: 0.51-0.96). CONCLUSIONS: Updated results from the MIG-1 study are numerically in favour of dose-dense chemotherapy, and suggest a long-term benefit of this approach in high-risk early breast cancer patients.

PICC-PORT totally implantable vascular access device in breast cancer patients undergoing chemotherapy.

BACKGROUND AND OBJECTIVES: The increasing use of arm totally implantable vascular access devices for breast cancer patients who require chemotherapy has led to a greater risk of complications and failures and, in particular, to upper extremity deep vein thrombosis. This study aims to investigate the outcomes of the arm peripherally inserted central catheter-PORT technique in breast cancer patients. METHODS: The peripherally inserted central catheter-PORT technique is an evolution of the standard arm-totally implantable vascular access device implant based on guided ultrasound venous access in the proximal third of the upper limb with subsequent placement of the reservoir at the middle third of the arm. A prospective study was conducted on 418 adult female breast cancer patients undergoing chemotherapy. The primary study outcome was peripherally inserted central catheter-PORT failure. RESULTS: Median follow-up was 215 days. Complications occurred in 29 patients (6.9%) and failure resulting in removal of the device in 11 patients (2.6%). The main complication we observed was upper extremity deep vein thrombosis, 10 (2.4%); all patients were rescued by anticoagulant treatment without peripherally inserted central catheter-PORT removal. The main reason for removal was reservoir pocket infection: 4 (0.9%) with an infection rate of 0.012 per 1000 catheter days. Cumulative 1-year risk of failure was 3.6% (95% confidence interval, 1.3%-7.1%). With regard to the patients' characteristics, body mass index <22.5 was the only significant risk for failure (p = 0.027). CONCLUSION: The peripherally inserted central catheter-PORT is a safe vascular device for chemotherapy delivery that achieves similar clinical results as traditional long-term vascular access devices (peripherally inserted central catheter and arm totally implantable vascular access device, in particular) in breast cancer patients.

T-DM1 Efficacy in Patients With HER2-positive Metastatic Breast Cancer Progressing After a Taxane Plus Pertuzumab and Trastuzumab: An Italian Multicenter Observational Study.

BACKGROUND: T-DM1 improves progression-free survival (PFS) and overall survival (OS) in patients with metastatic human epidermal growth factor receptor 2-positive (HER2+) breast cancer progressing on prior trastuzumab plus a taxane. A paucity of data is available on T-DM1 efficacy after dual anti-HER2 blockade with pertuzumab and trastuzumab plus a taxane, which represents the current first-line standard of care. The present study is a retrospective/prospective evaluation of the efficacy and activity of second-line T-DM1 after front-line pertuzumab-based therapy. PATIENTS AND METHODS: Eligible patients were identified within the Gruppo Italiano Mammella (GIM) 14/BIOMETA study, a retrospective/prospective multicenter study on treatment patterns and outcomes of patients with metastatic breast cancer (ClinicalTrials.gov Identifier: NCT02284581). We searched for patients who received second-line T-DM1 after taxane plus trastuzumab and pertuzumab between November 15, 2013 and May 31, 2018. We calculated median PFS, median time to treatment failure (TTF), prolonged duration of therapy (PDT), objective response rate (ORR), and 1-year OS. RESULTS: Of 445 patients with HER2+ metastatic breast cancer, 77 were eligible for the analysis. At a median follow-up of 7 months, median PFS was 6.3 months (95% confidence intervals [CI], 4.8-7.7 months), and median TTF was 6.2 months (95% CI, 4-8.6 months). More than one-third of patients (37.6%; n = 29) experienced PDT with an ORR of 27.1%. At data cutoff, the median OS was not reached, and the 1-year OS was 82%. CONCLUSIONS: Our results show meaningful activity of T-DM1 after front-line pertuzumab plus trastuzumab and a taxane, with about 27% of patients having an objective response and 40% of patients achieving durable disease control.

Potential Mechanisms of Ovarian Protection with Gonadotropin-Releasing Hormone Agonist in Breast Cancer Patients: A Review.

The use of chemotherapy in premenopausal cancer patients may lead to chemotherapy-induced premature ovarian failure. Pharmacological temporary ovarian suppression obtained with the gonadotropin-releasing hormone agonist (GnRHa) administered concomitantly with chemotherapy has been investigated as a technique capable to reduce the gonadotoxicity, reducing the risk of developing premature menopause. In recent years, important evidence has become available on the efficacy and safety of this strategy that should now be considered a standard option for ovarian function preservation in premenopausal breast cancer patients. However, in women interested in fertility preservation, this is not an alternative to cryopreservation strategies, which remains the first option to be proposed. The purpose of this review is to summarize the mechanisms of GnRHa in the preservation of fertility in premenopausal cancer patient candidates to receive chemotherapy, highlighting the areas of doubt that require further investigation.