Breast cancer is the most common cancer diagnosed among women worldwide and more than half are diagnosed above the age of 60 years. Life expectancy is increasing and the number of breast cancer cases diagnosed among older women are expected to increase. Undertreatment, mostly due to unjustifiable fears of advanced-age and associated comorbidities, is commonly practiced in this group of patients who are under-represented in clinical trials and their management is not properly addressed in clinical practice guidelines. With modern surgery and anesthesia, breast surgeries are considered safe and is usually associated with very low complication rates, regardless of extent of surgery. However, oncoplastic surgery and management of the axilla can be tailored based on patients’- and disease-related factors. Most of chemotherapeutic agents, along with targeted therapy and anti-Human epidermal growth factor receptor-2 (HER2) drugs can be safely given for older patients, however, dose adjustment and close monitoring of potential adverse events might be needed. The recently introduced cyclin-D kinase (CDK) 4/6-inhibitors in combination with aromatase inhibitors (AI) or fulvestrant, which changed the landscape of breast cancer therapy, are both safe and effective in older patients and had substituted more aggressive and potentially toxic interventions. Despite its proven efficacy, adjusting or even omitting adjuvant radiation therapy, at least in low-risk older patients, is safe and frequently practiced. In this paper, we review existing data related to breast cancer management among older patients across the continuum; from resection of the primary tumor through adjuvant chemotherapy, radiation and endocrine therapy up to the management of recurrent and advanced-stage disease.

Background: Genetic testing for at-risk patients with breast cancer should be routinely offered. Knowledge generated may influence both treatment decisions and cancer prevention strategies among the patients themselves and their relatives. In this study, we report on the prevalence and patterns of germline mutations, using commercially available next-generation sequencing (NGS)-based multi-gene panels (MGP). Patients and Methods: Consecutive at-risk breast cancer patients, as determined by international guidelines, were offered germline genetic testing using a 20-gene NGS-based panel at a reference lab. Samples of peripheral blood were obtained for DNA extraction and genetic variants were classified as benign/likely benign (negative), pathogenic/likely pathogenic (positive) or variants of uncertain significance (VUS). Results: A total of 1310 patients, median age (range) 43 (19– 82) years, were enrolled. Age ≤ 45 years (n = 800, 61.1%) was the most common indication for testing. Positive family history of breast, ovarian, pancreatic or prostate cancers, and triple-negative disease were among the common indications. Among the whole group, 184 (14.0%) patients had pathogenic/likely pathogenic variants; only 90 (48.9%) were in BRCA1 or BRCA2, while 94 (51.9%) others had pathogenic variants in other genes; mostly in APC, TP53, CHEK2 and PALB2. Mutation rates were significantly higher among patients with positive family history (p = 0.009); especially if they were 50 years or younger at the time of breast cancer diagnosis (p < 0.001). Patients with triple-negative disease had relatively higher rate (17.5%), and mostly in BRCA1/2 genes (71.4%). Variants of uncertain significance (VUS) were reported in 559 (42.7%) patients; majority (90.7%) were in genes other than BRCA1 or BRCA2. Conclusion: Pathogenic mutations in genes other than BRCA1/2 are relatively common and could have been missed if genetic testing was restricted to BRCA1/2. The significantly high rate of VUS associated with multi-gene panel testing can be disturbing.

Breast cancer radiotherapy has evolved significantly, driven by decades of research into fractionation schedules aimed at optimizing treatment efficacy and minimizing toxicity. Initial trials such as NSABP B‑06 and EBCTCG meta‑analyses established the benefits of adjuvant whole‑breast irradiation in reducing local recurrence and improving survival rates. The linear‑quadratic (LQ) model provided a framework to understand tissue response to radiation, highlighting the importance of the α/β ratio in determining fractionation sensitivity. The present scoping review aimed to identify and describe hypofractionation regimens for whole breast radiotherapy and evaluate dose differences using the LQ model across proposed α/β ratios. A comprehensive PubMed search for clinical trials published since 2010 on hypo‑fractionated regimens was performed. Studies discussing α/β ratios for breast cancer have been also searched. Data on dose, fractions and α/β ratios were collected, and biologically effective dose (BED) and equivalent dose in 2 Gy fractions were calculated. The coefficient of variation for BED varied with α/β ratios, showing the lowest variability for an α/β ratio of ~3 without tumor repopulation and increased with repopulation (BED‑kT; k is a constant that depends on the repopulation rate of the tumor, and T is the total treatment time in days). Significant differences in BED variances were observed across α/β ratios (F‑statistic 219.6, P<0.0001). START trials (P, A, and B) established α/β ratios of 3‑4 Gy for breast cancer and normal tissues, confirming that hypofractionation is as effective as standard fractionation with potentially fewer late toxicities. Subsequent trials, such as FAST and FAST‑Forward, demonstrated that ultra‑hypofractionation is equivalent in tumor compared with conventional regimens. Further research is needed to gain a stronger understanding of radiobiological properties of breast cancer cells. Advances in radiotherapy technologies and the integration of biomarkers, radiomics and genomics are transforming treatment, moving towards precision medicine.

The quality assurance (QA) chart rounds are multidisciplinary meetings to review radiation therapy (RT) treatment plans. This study focus on describing the changes in RT management based on QA round reviews in a single institution. After 9 full years of implementation, a retrospective review of all patients whose charts passed through departmental QA chart rounds from 2007 to 2015. The reviewed cases were presented for RT plan review; subcategorized based on decision in QA rounds into: approved, minor modifications or major modifications. Major modification defined as any substantial change which required patient re-simulation or re-planning prior to commencement of RT. Minor modification included treatment plan changes which didn't necessarily require RT re-planning. Overall 7,149 RT treatment plans for different anatomical sites were reviewed at QA rounds. From these treatment plans, 6,654 (93%) were approved, 144 (2%) required minor modifications, while 351 (5%) required major modifications. Major modification included changes in: selected RT dose (96/351, 27%), target volume definition (127/351, 36%), organs-at-risk contouring (10/351, 3%), dose volume objectives/constraints criteria (90/351, 26%), and intent of treatment (28/351, 8%). The RT plans which required major modification according to the tumor subtype were as follows: head and neck (104/904, 12%), thoracic (12/199, 6%), gastrointestinal (33/687,5%), skin (5/106, 5%), genitourinary (16/359, 4%), breast (104/2387, 4%), central nervous system (36/846, 4%), sarcoma (11/277, 4%), pediatric (7/251, 3%), lymphoma (10/423, 2%), gynecological tumors (2/359, 1%), and others (11/351, 3%). Multi-disciplinary standardized QA chart rounds provide a comprehensive and an influential method on RT plans and/ or treatment decisions.

Salvage re-irradiation (rRT) for patients with locoregionally recurrent head and neck cancer (rHNC) remains challenging. A retrospective analysis was performed on 49 patients who received rRT between 2011 and 2018. The co-primary endpoint of the study was 2-year freedom from cancer recurrence rate (FCRR) and overall survival (OS), and secondary endpoints were 2-year disease-free survival (DFS), local failure (LF), regional failure (RF), distant metastases (DM), and RTOG grade 3 ≥ late toxicities. Adjuvant and definitive rRT were delivered to 22 and 27 patients, respectively. A total of 91% of patients were managed with conventional re-RT and 71% of patients received concurrent chemotherapy. The median follow-up after rRT was 30 months. The 2-year FCRR, OS, DFS, LF, RF, and DM were 64%, 51%, 28%, 32%, 9%, and 39% respectively. MVA showed that poor performance status (PS: 1–2 vs. 0) and age > 52 years were predictive of worse OS. In comparison, poor PS (1–2 vs. 0) and total dose of rRT < 60 Gy were predictive of worse DFS. Late RTOG toxicity of grade 3 ≥ was reported in nine (18.3%) patients. FCRR at 2 years after salvage rRT for rHNC was higher than other traditional endpoints and could be an important endpoint to be included in future rRT studies. rRT for rHNC at our cohort was relatively successful, with a manageable level of late severe toxicity. Replacing this approach in other developing countries is a viable option.