Treatment selection for patients with equivocal HER2 status and in luminal versus HER2-enriched disease

Equivocal HER2 status has been variably defined in the past, and its clinical implications have long been debated. In the 2018 focused update, ASCO/CAP guidelines recommended that tumours with double-equivocal (by immunohistochemistry and in situ hybridization assays) HER2 status should be considered HER2-negative due to the lack of evidence for any benefit of HER2-targeted therapy. The biology and the response to systemic therapies of tumours co-expressing HR and HER2 is quite complex. There is an extensive bi-directional cross-talk between these 2 pathways, that may result in both intrinsic and acquired resistance to endocrine agents, as well as in lower sensitivity to HER2-targeted therapies. In fact, neoadjuvant studies indicate that pCR rates are significantly lower in HER2-positive/ER-positive than ER-negative tumours, regardless the type of HER2 targeted treatment. The recent identification of different subtypes of HER2-positive breast cancer, according to the co-expression of HR and/or the molecular (intrinsic) subtyping, has prompted a renewed interest for clinical studies aimed at better tailoring the systemic therapy for these patients. A subgroup of them might not need chemotherapy if treated with dual HER2 blockade, and this option has been tested in a number of neo-adjuvant trials. In addition, triple targeting of HR, HER2, and CDK4/6 pathways simultaneously may be an effective treatment and overcome the drug resistance mechanisms that are typical of the disease. Finally, HER2-positive breast cancer may well benefit from immunotherapeutic interventions with anti-programmed cell death protein 1 (PD-1) and programmed cell death ligand 1 (PD-L1) agents

Prognosis of selected triple negative apocrine breast cancer patients who did not receive adjuvant chemotherapy

Background: Triple negative breast cancer encompasses several biological entities with different outcomes and is a priority to identify which patients require more treatment to reduce the risk of recurrence and which patients need less treatment. Patients and methods: Among the 210 women with first primary invasive apocrine non metastatic breast cancer operated on between January 1998 and December 2016 at the European Institute Oncology, Milan, we identified 24 patients with a pT1-pT2, node-negative, triple negative subtype and Ki-67 64 20% who did not receive adjuvant chemotherapy (CT). We compared the outcome of this cohort with a similar group of 24 patients with ductal tumors who received adjuvant chemotherapy, matched by pathological stage and biological features and also with a similar group of 12 patients with apocrine tumors who received adjuvant chemotherapy. Results: The median age was 64 and 61 years in the apocrine (w/o CT) and ductal group, respectively. The median value of Ki-67 expression was 12% in the apocrine group (w/o CT) and 16% in the ductal group (p < 0.001). After a median follow-up of 7.5 years, no patients in the apocrine group (w/o CT) experienced a breast cancer related event compared with 4 events in the ductal carcinoma group (Gray test p-value = 0.11). Conclusions: The outcome of selected apocrine triple negative breast cancer patients who did not received adjuvant chemotherapy is excellent and supports a treatment de-escalation. Multicenter projects focusing on the possibility of avoiding adjuvant chemotherapy in selected subtypes of triple negative breast cancers with favorable outcome are warranted

metronomic administration of pegylated liposomal doxorubicin in extensively pre treated metastatic breast cancer patients a mono institutional case series report

Abstract Background Metronomic chemotherapy has shown efficacy in patients with metastatic breast cancer. Pegylated liposomal-doxorubicin (PLD) pharmacokinetic characteristics support the rationale for using the drug in a metronomic fashion, potentially able to combine anthracyclines efficacy to a low toxicity profile. Patients and methods In a case-series report carried out in both anthracycline-naive and pre-treated metastatic breast cancer patients, we tested feasibility, clinical efficacy and tolerability of PLD administered with a novel metronomic schedule of 20 mg/m2 i.v. every two weeks. Results 52 patients were enrolled and 45 were evaluated. Forty-four patients were assessed for either response or toxicity. Eight patients (18%) had partial responses (PR) and 17 (39%) stable disease (SD), with a clinical benefit (CB) of 45% (95% CI: 30.3%–59.7%). Nineteen patients (43%) had progressive disease (PD). Neither grade 3 nor grade 4 haematological or clinical side effects were recorded, except for 2 patients with grade 3 palmar-plantar erythrodysesthesia (PPE). No cardiac toxicity was recorded. Conclusion Metronomic administration of PLD is a feasible and active treatment for extensively pre-treated metastatic breast cancer patients, alternative to classic anthracyclines, balancing clinical efficacy with a good quality of life in terms of reduced side effects and low personal costs for the patient

Development and psychometric testing of a breast cancer patient-profiling questionnaire

Introduction: The advent of \u201cpersonalized medicine\u201d has been driven by technological advances in genomics. Concentration at the subcellular level of a patient\u2019s cancer cells has meant inevitably that the \u201cperson\u201d has been overlooked. For this reason, we think there is an urgent need to develop a truly personalized approach focusing on each patient as an individual, assessing his/her unique mental dimensions and tailoring interventions to his/her individual needs and preferences. The aim of this study was to develop and test the psychometric properties of the ALGA-Breast Cancer (ALGA-BC), a new multidimensional questionnaire that assesses the breast cancer patient\u2019s physical and mental characteristics in order to provide physicians, prior to the consultation, with a patient\u2019s profile that is supposed to facilitate subsequent communication, interaction, and information delivery between the doctor and the patient. Methods: The specific validation processes used were: content and face validity, construct validity using factor analysis, reliability and internal consistency using test\u2013retest reliability, and Cronbach\u2019s alpha correlation coefficient. The exploratory analysis included 100 primary breast cancer patients and 730 healthy subjects. Results: The exploratory factor analysis revealed eight key factors: global self-rated health, perceived physical health, anxiety, self-efficacy, cognitive closure, memory, body image, and sexual life. Test\u2013retest reliability and internal consistency were good. Comparing patients with a sample of healthy subjects, we also observed a general ability of the ALGA-BC questionnaire to discriminate between the two. Conclusion: The ALGA-BC questionnaire with 29 items is a valid instrument with which to obtain a patient\u2019s profile that is supposed to help physicians achieve meaningful personalized care which supplements biological and genetic analyse

Synergistic activity of oxaliplatin and 5-fluorouracil in patients with metastatic colorectal cancer with progressive disease while on or after 5-fluorouracil

From February 1995 through October 1996, 25 patients with metastatic colorectal cancer showing a clinical resistance to 5-fluorouracil (5-FU) entered this study. Thirteen received oxaliplatin alone and 12 received it in combination with 5-FU. Oxaliplatin was administered at 130 mg/m(2) over a 2-hour infusion every 3 weeks, alone or added either to 5-FU as a continuous infusion at 200 mg/m(2) to 300 mg/m(2) (six patients) or to a 5-FU bolus, 375 mg/m(2), plus leucovorin, 100 mg/m(2) daily for 5 days every 3 weeks (6 patients). Eighty-six of 98 administered cycles were evaluable for toxicity (47 for oxaliplatin plus 5-FU and 39 for oxaliplatin alone). Hematologic toxicity was mild, occurring as grade 2 leukopenia in 23% of the cycles of 5-FU and oxaliplatin and in 5% of the cycles of oxaliplatin alone. The most common toxicity was neurologic (grade 1 to 2 in 60%-6% of the cycles of the combination, respectively, and 68%-10% of oxaliplatin given alone) as hand-foot paresthesia or hypersensitivity to cold. No grade 4 toxicity was reported and only three patients in the 5-FU group developed grade 3 diarrhea. Grade 2 nausea and vomiting occurred in 33% of the cycles when both drugs were given and in 15% when oxaliplatin was administered alone. The combination of oxaliplatin and 5-FU induced four partial remissions (33%; 95% confidence interval, 6%-60%), whereas eight patients of the whole group had stable disease. No response occurred when oxaliplatin was administered as a single agent. The results of this study confirm the antitumor activity of oxaliplatin when added to 5-FU in patients who have metastatic colorectal cancer previously refractory to 5-FU. The possible therapeutic synergy with 5-FU was not accompanied by increased toxicity

Outcomes of special histotypes of breast cancer after adjuvant endocrine therapy with letrozole or tamoxifen in the monotherapy cohort of the BIG 1-98 trial

In the BIG 1-98 clinical trial of 4922 postmenopausal women treated with 5 years of letrozole or tamoxifen for endocrine-responsive breast cancer, 183 had the rare histotypes mucinous or tubular/cribriform. These women had better outcomes than those with other histotypes. The magnitude of the letrozole advantage compared with tamoxifen may not be as large in patients with these rare histotype

Long-term responders to trastuzumab monotherapy in first-line HER-2+ advanced breast cancer: characteristics and survival data.

The impact of HER2-targeted therapy alone followed by the addition of chemotherapy at disease progression (PD) versus upfront combination was investigated by the SAKK 22/99 trial. The aim of this exploratory analysis of the SAKK 22/99 trial was to characterize the specific subset of patients deriving long-term benefit from trastuzumab monotherapy alone and to identify potential predictive factors of long-term response. This is an unplanned post-hoc analysis of patients randomized to Arm A (trastuzumab monotherapy). Patients were divided in two groups: patients with durable clinical benefit from trastuzumab monotherapy and short-term responders without durable clinical benefit from trastuzumab monotherapy Univariate and multivariate analyses of clinical characteristics correlating with response duration was performed. Eighty six patients were randomized in arm A, 24 patients (28%) were long-term responders and 62 (72%) were short-term responders with a 5y-overall survival (OS) of 54% (95% CI 31-72) and of 18% (95%CI 10-30), respectively. Absence of ER expression, absence of PgR expression and presence of visceral disease emerged as possible negative predictive factors for durable clinical benefit. Durable clinical benefit can be achieved with trastuzumab monotherapy in a subgroup of HER2-positive patients with advanced disease and it is predictive for longer OS. Further investigations of predictive biomarkers are necessary to better characterize this subgroup of patients and develop further de-escalating strategies. NCT00004935 ; first posted 27.01.2003, retrospectively registered

Outcome and clinico-biological characteristics of advanced breast cancer patients with surgically resected brain metastases : a multidisciplinary approach

Background: Despite improvements in brain surgery and radiotherapy, patients with brain metastases (BM) from breast cancer still have a poor prognosis. The aim of the present study is to evaluate the outcome of a multimodal therapeutic strategy in an unselected cohort of patients. Methods: We retrospectively reviewed 24 breast cancer patients who developed BM and were treated with brain surgery, radiotherapy, and/or systemic therapy in the same institutions. Results: Primary treatment for BM was surgery in the whole cohort, radiotherapy in 11 patients, radiotherapy combined with systemic therapy in nine patients, and systemic therapy as single treatment in six patients (chemo/targeted therapy n= 4; hormonal therapy n=2). The median time from breast cancer diagnosis to brain surgery was 57.6 months (range 1.8\u2013130.7 months). The overall survival from surgery for BM was 22 months and the overall survival from BM surgery by presence of other metastatic sites at surgery was 25 months for patients with BM only and 11 months for patients with other metastatic sites (p=0.046). Conclusion: Although this study is retrospective and limited by the small number of patients, the overall survival of 22 months from the time of brain surgery represents an excellent outcome. The multidisciplinary approach that combines the efforts of specialists from different disciplines leads to satisfactory results for patients in terms of survival in the current clinical practice and prospective subtype-oriented trials are urgently required in this category of patients