Metastatic Occult Primary Lobular Breast Cancer: A Case Report.

Breast cancer is the most common malignancy diagnosed in women. Invasive lobular breast cancer (ILC) is the second most common histologic subtype after invasive ductal carcinoma. Metastatic occult primary breast cancer, although rare, is a well-known clinical entity that usually presents with axillary lymphadenopathy without a detectable breast tumour. A perimenopausal woman in her 50s presented with abdominal pain, fatigue, and weight loss. Imaging showed peritoneal carcinomatosis with ascites, ovarian masses, and a lesion in the ascending colon. Gastric and colon biopsies showed infiltration from lobular breast cancer. Diagnostic workup, including mammography, breast ultrasound, and breast MRI, showed no evidence of breast pathology or axillary lymphadenopathy. First-line treatment with goserelin, letrozole, and palbociclib commenced with clinical improvement and radiological response. This case illustrates the challenges faced by clinicians in the diagnosis and treatment of lobular breast cancer without an identifiable primary lesion or axillary lymphadenopathy.

Effectiveness of a Computerized Home-Based Cognitive Stimulation Program for Treating Cancer-Related Cognitive Impairment.

Cancer patients assert that after chemotherapy their cognitive abilities have deteriorated. Cognitive stimulation is the clinical treatment of choice for reversing cognitive decline. The current study describes a computerized home-based cognitive stimulation program in patients who survived breast cancer. It aims to assess safety and effectiveness of cognitive stimulation in the oncology population. A series of 45-min training sessions was completed by the participants. A thorough assessment was performed both before and after the intervention. The mini-Mental Adjustment to Cancer Scale, the Cognitive Assessment for Chemo Fog Research, and the Functionality Assessment Instrument in Cancer Treatment-Cognitive Function served as the main assessment tools. The State-Trait Anxiety Inventory, Beck Depression Inventory, Brief Fatigue Inventory, and Measuring Quality of Life-The World Health Organization data were gathered as secondary outcomes. Home-based cognitive stimulation demonstrated beneficial effects in the oncology population, with no side effects being reported. Cognitive, physical, and emotional improvements were observed, along with decreased interference in daily life activities and a better overall quality of life.

Trifluridine/Tipiracil in Metastatic Colorectal Cancer: A UK Multicenter Real-world Analysis on Efficacy, Safety, Predictive and Prognostic Factors.

BACKGROUND: The orally administered combination trifluridine/tipiracil has been approved as third line treatment in mCRC, demonstrating survival benefit and acceptable toxicity profile in the phase III RECOURSE study. PATIENT AND METHODS: We performed a multicenter retrospective real-world analysis of patients with mCRC receiving trifluridine/tipiracil between 2016 and 2019 in eight cancer centers across the United Kingdom. RESULTS: A total of 236 patients were included with median age of 69 years. All patients had received at least 2 lines of fluoropyrimidine-based chemotherapy doublet with oxaliplatin or irinotecan. About 10% of patients had ECOG ≥ 2. Median duration of trifluridine/tipiracil treatment was 3 months with an ORR of 2.1% and disease control rate of 21.6%. Median OS was 7.6 and median PFS 3.3 months. A dose reduction was required in 27% of patients, while 7.6% discontinued treatment due to toxicity. The most common grade 3 toxicities were neutropenia (34%), fatigue (10%), anemia (9%) and febrile neutropenia (5%). Baseline NLR <5 and CEA <200 had favorable prognostic (HR: 0.52 and 0.39, P≤ .001) and predictive value (OR: 4.1 and 6.7, P< .05). Development of grade 3 neutropenia predicted treatment response (OR: 0.32, P< .001). Following treatment with trifluridine/tipiracil 41% were referred for phase I trial or rechallenged with chemotherapy. CONCLUSION: Trifluridine/tipiracil is well tolerated in refractory mCRC patients with comparable efficacy and toxicity profile to that of the phase III RECOURSE. Pretreatment NLR and CEA could serve as potential markers for patient selection, while treatment-induced grade 3 neutropenia predicted response. Prospective validation is needed.

Cardiac safety of neoadjuvant chemotherapy with epirubicin and cyclophosphamide followed by docetaxel/pertuzumab/trastuzumab for HER2-positive breast cancer patients.

PURPOSE: Early-stage, HER2-positive breast cancer is increasingly treated with neoadjuvant chemotherapy (NAC). After the positive results of the Neosphere trial, the standard of care has been the combination of chemotherapy with two anti-HER2 agents, trastuzumab and pertuzumab. Many oncologists use the sequence of four cycles of anthracycline-containing regimen followed by four cycles of taxane with the two monoclonals. We report here the cardiac safety of four cycles of epirubicin with cyclophosphamide followed by four cycles of docetaxel with trastuzumab and pertuzumab, given at the neoadjuvant setting in early, HER2-positive breast cancer. METHODS: We retrospectively collected data from the medical records of patients treated at our clinic between 2014 and 2020. RESULTS: It total, 55 patients treated with the same regimen were identified. There were 20 estrogen receptor (ER)-negative and 35 ER-positive patients. Complete pathologic response was observed in 64.8% of the patients. After a median cardiac follow-up of 2.61 years, and a total of 283 echocardiograms, there was only one recorded asymptomatic Left Ventricular Ejection Fraction (LVEF) fall > 25% and no symptomatic left ventricular systolic dysfunction. LVEF consistently dropped during treatment, but the drop was not significant enough to necessitate treatment interruption, and improved during follow-up. CONCLUSION: Our data confirm the effectiveness and cardiac safety of the aforementioned neoadjuvant regimen.

Surgical and Systemic Treatment of Hereditary Breast Cancer: A Mini-Review With a Focus on BRCA1 and BRCA2 Mutations.

Hereditary breast cancer accounts for 5%-10% of breast cancer cases. The majority of familial cases have been linked to germline mutations in BRCA1 and BRCA2 genes, though other high penetrance susceptibility genes have also been identified through genomic testing advances. Optimal surgical treatment for these patients, who are of a younger age, has several challenges as it usually involves aggressive therapeutic and risk reducing interventions. At the same time, the therapeutic armamentarium for BRCA1/2 mutation carriers apart from platinum salts, has been enriched with the addition of poly-ADP ribose polymerase (PARP) inhibitors with promising outcomes. In this review we provide a succinct and comprehensive overview of the surgical and systemic treatment options for patients with BRCA1/2 mutation related breast cancer and an update on the most recent systemic treatment advances.

Biliary Tract Cancers: Molecular Heterogeneity and New Treatment Options.

Most patients with biliary tract cancer (BTC) are diagnosed with advanced disease, relapse rates are high in those undergoing surgery and prognosis remains poor, while the incidence is increasing. Treatment options are limited, and chemotherapy is still the standard of care in both adjuvant and advanced disease setting. In recent years, different subtypes of BTC have been defined depending on the anatomical location and genetic and/or epigenetic aberrations. Especially for intrahepatic cholangiocarcinoma (iCCA) novel therapeutic targets have been identified, including fibroblast growth factor receptor 2 gene fusions and isocitrate dehydrogenase 1 and 2 mutations, with molecularly targeted agents having shown evidence of activity in this subgroup of patients. Additionally, other pathways are being evaluated in both iCCA and other subtypes of BTC, alongside targeting of the immune microenvironment. The growing knowledge of BTC biology and molecular heterogeneity has paved the way for the development of new therapeutic approaches that will completely change the treatment paradigm for this disease in the near future. This review provides an overview of the molecular heterogeneity of BTC and summarizes new targets and emerging therapies in development. We also discuss resistance mechanisms, open issues, and future perspectives in the management of BTC.

Real-world experience of neoadjuvant chemotherapy for early breast cancer patients: an observational non-interventional study in Thessaloniki, Greece.

PURPOSE: Neoadjuvant chemotherapy has been increasingly used in early-stage breast cancer. The results of large randomized clinical trials suggest the need for the wider use of preoperative therapy as it can result in a more conservative surgery, and can guide physicians to a more individualized approach in the adjuvant setting. METHODS: We aimed to analyze the outcomes of 203 patients with early-stage breast cancer who had received neoadjuvant chemotherapy at our institutions. RESULTS AND CONCLUSION: Pathological complete responses (pCR) were obtained in 42.4% of all patients, with the highest percentage in hormonal receptor (HR)-negative and human epidermal growth factor receptor-2 (HER2)-positive cancers. Conversion of a clinically and/or cytologically node-positive to node-negative disease was achieved in 55.8% of patients. Patients who achieved a pCR had a significantly better outcome in terms of disease-free and distant disease-free survival. Patients with residual disease experienced a worse prognosis if they had HR-negative cancer compared to HR-positive patients for whom the use of adjuvant endocrine treatment likely led to better outcomes. These results are encouraging as they show that outcomes from large randomized clinical trials can be reproduced in the everyday clinical setting. Neoadjuvant chemotherapy may be the treatment of choice for HR-negative and/or HER2-positive early breast cancer patients. This may also be the case for the majority of HR-positive and HER2-negative patients with either locally advanced disease or disease extending to the axillary lymph nodes, as it may result in more conservative surgical interventions with fewer post-operative complications.

Clinical implementation of pre-treatment DPYD genotyping in capecitabine-treated metastatic breast cancer patients.

PURPOSE: Metastatic breast cancer (mBC) patients with DPYD genetic variants linked to loss of dihydropyrimidine dehydrogenase (DPD) activity are at risk of severe capecitabine-associated toxicities. However, prospective DPYD genotyping has not yet been implemented in routine clinical practice. Following a previous internal review in which two patients underwent lengthy hospitalisations whilst receiving capecitabine, and were subsequently found to be DPD deficient, we initiated routine DPYD genotyping prior to starting capecitabine. This study evaluates the clinical application of routine DPYD screening at a large cancer centre in London. METHODS: We reviewed medical records for consecutive patients with mBC who underwent DPYD genotyping before commencing capecitabine between December 2014 and December 2017. Patients were tested for four DPYD variants associated with reduced DPD activity. RESULTS: Sixty-six patients underwent DPYD testing. Five (8.4%) patients were found to carry DPYD genetic polymorphisms associated with reduced DPD activity; of these, two received dose-reduced capecitabine. Of the 61 patients with DPYD wild-type, 14 (23%) experienced grade 3 toxicities which involved palmar-plantar erythrodysesthesia (65%), and gastrointestinal toxicities (35%); no patient was hospitalised due to toxicity. CONCLUSIONS: Prospective DPYD genotyping can be successfully implemented in routine clinical practice and can reduce the risk of severe fluoropyrimidine toxicities.