Long-Term Outcomes of Adjuvant Trastuzumab for 9 Weeks or 1 Year for ERBB2-Positive Breast Cancer: A Secondary Analysis of the SOLD Randomized Clinical Trial.

Importance: The standard adjuvant treatment for patients with ERRB2-positive breast cancer is chemotherapy plus 1 year of trastuzumab. Shorter durations of trastuzumab administration improve cardiac safety, but more information is needed about their effect on survival. Objective: To compare survival outcomes after 9-week vs 1-year administration of trastuzumab with the same adjuvant chemotherapy. Design, Setting, and Participants: This post hoc secondary analysis of an open-label, multicenter, noninferiority-design randomized clinical trial included women aged 18 years or older with early ERBB2-positive, axillary node-negative or axillary node-positive breast cancer who were enrolled from January 3, 2008, to December 16, 2014, at 65 centers in 7 European countries. The current exploratory analysis was conducted after achieving the maximum attainable follow-up data when the last patient enrolled had completed the last scheduled visit in December 2022. Intervention: Chemotherapy consisted of 3 cycles of docetaxel administered at 3-week intervals followed by 3 cycles of fluorouracil, epirubicin, and cyclophosphamide at 3-week intervals. Trastuzumab was administered in both groups for 9 weeks concomitantly with docetaxel. In the 9-week group, no further trastuzumab was administered after chemotherapy, whereas in the 1-year group, trastuzumab was continued after chemotherapy to complete 1 year of administration. Main Outcomes and Measures: The primary objective was disease-free survival (DFS). Distant DFS and OS were secondary objectives. Survival between groups was compared using the Kaplan-Meier method and log-rank test or univariable Cox proportional hazards regression. Results: Among the 2174 women analyzed, median age was 56 years (IQR, 48-64 years). The median follow-up time was 8.1 years (IQR, 8.0-8.9 years); 357 DFS events and 176 deaths occurred. Trastuzumab for 9 weeks was associated with shorter DFS compared with trastuzumab for 1 year (hazard ratio [HR], 1.36; 90% CI, 1.14-1.62); 10-year DFS was 80.3% in the 1-year group vs 78.6% in the 9-week group. The 5-year and 10-year OS rates were comparable between the 9-week and 1-year groups (95.0% vs 95.9% and 89.1% vs 88.2%, respectively; HR for all time points, 1.20; 90% CI, 0.94-1.54). In multivariable analyses, 9-week treatment was associated with shorter DFS compared with 1-year treatment (HR for recurrence or death, 1.36; 95% CI, 1.10-1.68; P = .005), but there was no between-group difference in OS (HR, 1.22; 95% CI, 0.90-1.64; P = .20). Only 4 patients (0.2%) died of a cardiac cause. Conclusions and Relevance: In this secondary analysis of a randomized clinical trial, 1-year vs 9-week adjuvant trastuzumab was associated with improved DFS among patients with ERRB2-positive breast cancer receiving chemotherapy, but there was no significant difference in OS between the groups. Trial Registration: ClinicalTrials.gov Identifier: NCT00593697.

Evaluation of multiple transcriptomic gene risk signatures in male breast cancer.

Male breast cancer (BCa) is a rare disease accounting for less than 1% of all breast cancers and 1% of all cancers in males. The clinical management is largely extrapolated from female BCa. Several multigene assays are increasingly used to guide clinical treatment decisions in female BCa, however, there are limited data on the utility of these tests in male BCa. Here we present the gene expression results of 381 M0, ER+ve, HER2-ve male BCa patients enrolled in the Part 1 (retrospective analysis) of the International Male Breast Cancer Program. Using a custom NanoString™ panel comprised of the genes from the commercial risk tests Prosigna®, OncotypeDX®, and MammaPrint®, risk scores and intrinsic subtyping data were generated to recapitulate the commercial tests as described by us previously. We also examined the prognostic value of other risk scores such as the Genomic Grade Index (GGI), IHC4-mRNA and our prognostic 95-gene signature. In this sample set of male BCa, we demonstrated prognostic utility on univariate analysis. Across all signatures, patients whose samples were identified as low-risk experienced better outcomes than intermediate-risk, with those classed as high risk experiencing the poorest outcomes. As seen with female BCa, the concordance between tests was poor, with C-index values ranging from 40.3% to 78.2% and Kappa values ranging from 0.17 to 0.58. To our knowledge, this is the largest study of male breast cancers assayed to generate risk scores of the current commercial and academic risk tests demonstrating comparable clinical utility to female BCa.

Managing vulvovaginal atrophy after breast cancer.

Cancer treatment may result in loss of ovarian function through surgical removal of the ovaries, chemotherapy or radiation. While menopausal symptoms, such as hot flushes, night sweats, sleep disturbance, memory concerns and mood issues can be extremely bothersome to some women going through menopause naturally, women who undergo an induced menopause usually experience more sudden and severe symptoms. Pain and vaginal dryness can occur whether a woman has a sexual partner or not. In women with breast cancer, the aetiology of impaired sexual functioning, and lowered sexual desire, is often multifactorial, and may be related to physical and/or psychological reasons. Pain and vaginal dryness in women without a history of breast cancer can usually be safely treated with vaginal estrogens, in the form of a cream, pessary or ring, and simple lubricants or vaginal moisturisers. Safe usage of vaginal estrogen replacement therapy in breast cancer patients has not been studied within randomised clinical trials of long duration; the guidelines below reflect a clinical consensus.

Effect of Adjuvant Trastuzumab for a Duration of 9 Weeks vs 1 Year With Concomitant Chemotherapy for Early Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: The SOLD Randomized Clinical Trial.

Importance: Trastuzumab plus chemotherapy is the standard adjuvant treatment for patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer. While the standard duration of trastuzumab treatment is 12 months, the benefits and harms of trastuzumab continued beyond the chemotherapy are unclear. Objective: To evaluate the efficacy and safety of adjuvant trastuzumab continued beyond chemotherapy in women treated with up-front chemotherapy containing a taxane and trastuzumab. Design, Setting, and Participants: Open-label, randomized (1:1) clinical trial including women with HER2-positive breast cancer. Chemotherapy was identical in the 2 groups, consisting of 3 cycles of 3-weekly docetaxel (either 80 or 100 mg/m2) plus trastuzumab for 9 weeks, followed by 3 cycles of fluorouracil, epirubicin, and cyclophosphamide. Thereafter, no trastuzumab was administered in the 9-week group, whereas controls received trastuzumab to complete 1 year of administration. Disease-free survival (DFS) was compared between the groups using a Cox model and the noninferiority approach. The estimated sample size was 2168 patients (1-sided testing, with a relative noninferiority margin of 1.3). From January 3, 2008, to December 16, 2014, 2176 patients were accrued from 7 countries. Intervention: Docetaxel plus trastuzumab for 9 weeks, followed by 3 cycles of fluorouracil, epirubicin, and cyclophosphamide in both groups. Controls continued trastuzumab to 1 year. Main Outcomes and Measures: The primary objective was DFS; secondary objectives included distant disease-free survival, overall survival, cardiac DFS, and safety. Results: In the 2174 women analyzed, median age was 56 (interquartile range [IQR], 48-64) years. The median follow-up was 5.2 (IQR, 3.8-6.7) years. Noninferiority of the 9-week treatment could not be demonstrated for DFS (hazard ratio, 1.39; 2-sided 90% CI, 1.12-1.72). Distant disease-free survival and overall survival did not differ substantially between the groups. Thirty-six (3%) and 21 (2%) patients in the 1-year and the 9-week groups, respectively, had cardiac failure; the left ventricle ejection fraction was better maintained in the 9-week group. An interaction was detected between the docetaxel dose and DFS; patients in the 9-week group treated with 80 mg/m2 had inferior and those treated with 100 mg/m2 had similar DFS as patients in the 1-year group. Conclusions and Relevance: Nine weeks of trastuzumab was not noninferior to 1 year of trastuzumab when given with similar chemotherapy. Cardiac safety was better in the 9-week group. The docetaxel dosing with trastuzumab requires further study. Trial Registration: ClinicalTrials.gov Identifier: NCT00593697.

Head louse and other common infections in schools: head teachers' use of an information pack.

A descriptive study examined head teachers' use of an information pack about common childhood infections and its usefulness, particularly for head louse infection. The survey covered all 122 schools in one borough in the North West of England. Overall response was 73% and 83.3% of head teachers considered the pack helpful for teachers and parents. The study highlights schools' wish for information and help with common infections, especially head louse infections, from the public health and community health services. The authors recommend providing such information regularly each term or year for teachers and parents, putting head louse infection in context with other common childhood infections. Regular education sessions are recommended for head teachers and community health professionals involved with head louse infections. These measures should help ensure a consistent, evidence-based and up-to-date approach.

Are patients in clinical trials representative of the general population? Dose intensity and toxicities associated with FE100C-D chemotherapy in a non-trial population of node positive breast cancer patients compared with PACS-01 trial group.

PURPOSE: In our institution, adjuvant taxanes are currently offered to fit, node positive breast cancer patients who are either Her2 positive (any ER/PR) or triple negative (ER/PR/Her2 negative). The FE(100)C-D (FE(100)C × 3→docetaxel 100mg/m(2) × 3) regime, based on the PACS 01 trial [Roche H, Fumoleau P, Spielmann M, et al. Sequential Adjuvant Epirubicin-Based and Docetaxel Chemotherapy for node positive Breast Cancer Patients: The FNCLCC PACS 01 Trial. J Clin Oncol 2006;24:5664-5671] is used. We retrospectively audited our experience with FE(100)C-D at The Beatson West of Scotland Cancer Centre and one representative district general hospital (DGH), Falkirk and District Royal Infirmary (FDRI). PATIENTS AND METHODS: Over a two year period, 101 patients commenced adjuvant FE(100)C-D chemotherapy. Data was matched with the FE(100)C-D arm of the PACS 01 trial. RESULTS: Median age was 54 years. Twenty-six patients (26%) had ≥ 1 episode of febrile neutropaenia (FN), including one fatal episode. Twenty-nine percent of patients required treatment interruption ≥ 1 week. Thirty percent of patients had dose reductions. Thirty percent of patients received <90% dose intensity of docetaxel. CONCLUSION: The FN rate was substantially higher and docetaxel dose intensity substantially lower in our unselected sample of patients than in the reference study.(1) This 'real-life' data illustrates the problems of applying clinical trial data to the more generalised patient population.

Emerging drugs in colorectal cancer.

A raft of novel agents with different modes of action is finally challenging the position of 5-fluorouracil (5-FU) as the gold standard treatment for colorectal cancer. Oral fluoropyrimidines, topoisomerase I inhibitors and new generation platinum compounds are all currently being investigated. There is also increasing interest in the development and use of biological therapies, which may allow treatments to become tailored to individual patients and cause less toxicity than conventional cytotoxics. It is hoped that with the development of these new drugs, the response rates and survival for patients with colorectal cancer will improve from the poor prognosis that many face at present.