Primary breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Summary Background The Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial was designed to compare the efficacy and safety of anastrozole (1 mg) with tamoxifen (20 mg), both given orally every day for 5 years, as adjuvant treatment for postmenopausal women with early-stage breast cancer. In this analysis, we assess the long-term outcomes after a median follow-up of 120 months. Methods We used a proportional hazards model to assess the primary endpoint of disease-free survival, and the secondary endpoints of time to recurrence, time to distant recurrence, incidence of new contralateral breast cancer, overall survival, and death with or without recurrence in all randomised patients (anastrozole n=3125, tamoxifen n=3116) and hormone-receptor-positive patients (anastrozole n=2618, tamoxifen n=2598). After treatment completion, we continued to collect data on fractures and serious adverse events in a masked fashion (safety population: anastrozole n=3092, tamoxifen n=3094). This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN18233230. Findings Patients were followed up for a median of 120 months (range 0–145); there were 24 522 woman-years of follow-up in the anastrozole group and 23 950 woman-years in the tamoxifen group. In the full study population, there were significant improvements in the anastrozole group compared with the tamoxifen group for disease-free survival (hazard ratio [HR] 0·91, 95% CI 0·83–0·99; p=0·04), time to recurrence (0·84, 0·75–0·93; p=0·001), and time to distant recurrence (0·87, 0·77–0·99; p=0·03). For hormone-receptor-positive patients, the results were also significantly in favour of the anastrozole group for disease-free survival (HR 0·86, 95% CI 0·78–0·95; p=0·003), time to recurrence (0·79, 0·70–0·89; p=0·0002), and time to distant recurrence (0·85, 0·73–0·98; p=0·02). In hormone-receptor-positive patients, absolute differences in time to recurrence between anastrozole and tamoxifen increased over time (2·7% at 5 years and 4·3% at 10 years) and recurrence rates remained significantly lower on anastrozole than tamoxifen after treatment completion (HR 0·81, 95% CI 0·67–0·98; p=0·03), although the carryover benefit was smaller after 8 years. There was weak evidence of fewer deaths after recurrence with anastrozole compared with tamoxifen treatment in the hormone-receptor-positive subgroup (HR 0·87, 95% CI 0·74–1·02; p=0·09), but there was little difference in overall mortality (0·95, 95% CI 0·84–1·06; p=0·4). Fractures were more frequent during active treatment in patients receiving anastrozole than those receiving tamoxifen (451 vs 351; OR 1·33, 95% CI 1·15–1·55; p vs 112; OR 0·98, 95% CI 0·74–1·30; p=0·9). Treatment-related serious adverse events were less common in the anastrozole group than the tamoxifen group (223 anastrozole vs 369 tamoxifen; OR 0·57, 95% CI 0·48–0·69; p vs 78; OR 0·84, 95% CI 0·60–1·19; p=0·3). No differences in non-breast cancer causes of death were apparent and the incidence of other cancers was similar between groups (425 vs 431) and continue to be higher with anastrozole for colorectal (66 vs 44) and lung cancer (51 vs 34), and lower for endometrial cancer (six vs 24), melanoma (eight vs 19), and ovarian cancer (17 vs 28). No new safety concerns were reported. Interpretation These data confirm the long-term superior efficacy and safety of anastrozole over tamoxifen as initial adjuvant therapy for postmenopausal women with hormone-sensitive early breast cancer. Funding AstraZeneca.

/pdf/effect-of-anastrozole-and-tamoxifen-as-adjuvant-treatment-15bs3c6mfc.pdf

Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 10-year analysis of the ATAC trial.

Ductal carcinoma in situ (DCIS) of the breast represents a heterogeneous group of neoplastic lesions in the breast ducts. The goal for management of DCIS is to prevent the development of invasive breast cancer. This manuscript focuses on the NCCN Guidelines Panel recommendations for the workup, primary treatment, risk reduction strategies, and surveillance specific to DCIS.

https://www.unitypoint.org/desmoines/filesimages/Cancer%20Education/Oncology%20Nursing%20Conference/2015/2014%20NCCN%20Clin%20Pract%20Guidelines%20Male%20Sex%20Dysf.pdf

Clinical practice guidelines in oncology

Over the past decade, whole genome sequencing and other 'omics' technologies have defined pathogenic driver mutations to which tumor cells are addicted. Such addictions, synthetic lethalities and other tumor vulnerabilities have yielded novel targets for a new generation of cancer drugs to treat discrete, genetically defined patient subgroups. This personalized cancer medicine strategy could eventually replace the conventional one-size-fits-all cytotoxic chemotherapy approach. However, the extraordinary intratumor genetic heterogeneity in cancers revealed by deep sequencing explains why de novo and acquired resistance arise with molecularly targeted drugs and cytotoxic chemotherapy, limiting their utility. One solution to the enduring challenge of polygenic cancer drug resistance is rational combinatorial targeted therapy.

/pdf/combinatorial-drug-therapy-for-cancer-in-the-post-genomic-1zc101i0z5.pdf

Combinatorial drug therapy for cancer in the post-genomic era

https://www.ganjoho.org/knowledge/St.Gallen/St._Gallen2007.pdf

Progress and promise: highlights of the international expert consensus on the primary therapy of early breast cancer 2007

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(07)60200-1.pdf

Survival and safety of exemestane versus tamoxifen after 2–3 years' tamoxifen treatment (Intergroup Exemestane Study): a randomised controlled trial

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Survival and safety of exemestane versus tamoxifen after 2–3 years' tamoxifen treatment (Intergroup Exemestane Study): a randomised controlled trial