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Breast cancer (BC) patients are frequently at risk of developing other malignancies following treatment. Although studies have been conducted to elucidate the etiology of multiple primary malignancies (MPM) after a BC diagnosis, few studies have investigated other previously diagnosed primary malignancies (OPPM) before BC. Here, genome-wide profiling was used to identify potential driver DNA copy number alterations and somatic mutations that promote the development of MPMs. To compare the genomic profiles for two primary tumors (BC and OPPM) from the same patient, tumor pairs from 26 young women (≤50 years) diagnosed with one or more primary malignancies before breast cancer were analyzed. Malignant melanoma was the most frequent OPPM, followed by gynecologic- and hematologic malignancies. However, significantly more genetic alterations were detected in BC compared to the OPPM. BC also showed more genetic similarity as a group than the tumor pairs. Clonality testing showed that genetic alterations on chromosomes 1, 3, 16, and 19 were concordant in both tumors in 13 patients. TP53 mutations were also found to be prevalent in BC, MM, and HM. Although all samples were classified as genetically unstable, chromothripsis-like patterns were primarily observed in BC. Taken together, few recurrent genetic alterations were identified in both tumor pairs that can explain the development of MPMs in the same patient. However, larger studies are warranted to further investigate key driver mutations associated with MPMs., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Purpose: Multiple primary malignancies (MPMs) caused by breast cancer treatment are well described, but only few studies to date describe which other previous primary malignancies (OPPMs) occur before breast cancer. The purpose of the present study was to evaluate the prevalence of OPPMs in patients with breast cancer between 2007 and 2018 in Western Sweden., Methods: Patient selection was performed using both pathology reports at Sahlgrenska University Hospital (Sweden) and the Swedish Cancer Registry. All newly diagnosed breast cancer patients were screened for presence of OPPM., Results: In total, 8031 breast cancer patients were diagnosed at Sahlgrenska University Hospital between 2007 and 2018. The prevalence of breast cancer patients with OPPMs (n = 414) increased from on average 2.6% to 8.2% during this 12-year period and ranged from 17 to 59 patients annually. The most striking increase in prevalence was found among the gynecological tumors (endometrium and ovarian adenocarcinomas), malignant melanomas and gastrointestinal malignancies. These findings were validated using data of the Swedish Cancer Registry., Conclusions: The overall survival rates for cancer patients have improved tremendously during the past 40 years, in part due to individually tailored therapies and screening programs. Our study revealed an increasing trend of OPPMs in breast cancer patients.

Background: Current prognostic markers cannot adequately predict the clinical outcome of breast cancer patients. Therefore, additional biomarkers need to be included in routine immune panels. FOXA1 was a significant predictor of favorable outcome in primary breast cancer, while Nestin expression is preferentially found in triple-negative tumors with increased rate of nodal metastases, and reduced survival. No studies have investigated the prognostic value of FOXA1 and Nestin expression in breast cancer metastases., Methods: Breast cancer metastases (n = 164) from various anatomical sites were retrospectively analyzed by immunohistochemistry for FOXA1, Nestin and GATA3 expression. Cox regression analysis assessed the prognostic value of FOXA1 and Nestin expression., Results: In breast cancer metastases, FOXA1 expression was associated with Nestin-negativity, GATA3-positivity, ER-positivity, HER2-positivity and non-triple-negative status (P < 0.05). In contrast, Nestin expression was associated with FOXA1-negative, GATA3-negative, ER-negative, and triple-negative metastases (P < 0.05). Univariate Cox regression analysis showed FOXA1 expression was predictive of overall survival (OS, P = 0.00048) and metastasis-free survival (DMFS, P = 0.0011), as well as, distant metastasis-free survival in ER-positive patients (P = 0.036) and overall survival in ER-negative patients (P = 0.024). Multivariate analysis confirmed the significance of FOXA1 for both survival endpoints in metastatic breast cancer patients (OS, P = 0.0033; DMFS, P = 0.015)., Conclusions: In our study, FOXA1 was expressed mostly in ER-positive breast cancer metastases. Expression of Nestin was related to triple-negative metastases, where brain was the most frequent metastatic site. These findings highlight the clinical utility of FOXA1 and Nestin expression and warrant their inclusion in routine immunohistochemical panels for breast carcinoma.

The number of patients with multiple primary malignancies has been increasing steadily in recent years. In the present study, we describe a unique case of an 81-year-old woman with 5 metachronous and synchronous primary malignant neoplasms. The patient was first diagnosed with an endometrium adenocarcinoma in 1997 and a colon adenocarcinoma in 2002. Eleven years after her colon surgery, in 2013, the patient presented with 3 other primary malignancies within a 4-month time span: an invasive malignant melanoma on the lower leg, an invasive mucinous breast carcinoma in the right breast, and a pleomorphic spindle cell sarcoma on the left upper arm. Subsequent routine medical checkups in 2013-2017 revealed no metastases of the primary malignancies. The patient mentioned a familial aggregation of malignant tumors, including 2 sisters with breast cancer and a brother with lung cancer. Interestingly, next-generation sequencing analysis of the patient's blood sample detected no mutations in the BRCA1, BRCA2, TP53, PTEN, CDH1, PALB2, RAD51C, RAD51D, MLH1, MSH2, MSH6, PMS2, EPCAM, APC, MUTYH, STK11, BMPR1A, SMAD4, PTEN, POLE, POLD1, GREM1, and GALNT12 genes. Therefore, whole genome sequencing is warranted to identify cancer-related genetic alterations in this patient with quintuple primary malignancies.

Background and Purpose: Health related quality of life (HRQoL) was assessed in the randomised, prospective ARTSCAN study comparing conventional radiotherapy (CF) with accelerated radiotherapy (AF) for head and neck cancer., Material and Methods: 750 patients with squamous cell carcinoma (of any grade and stage) in the oral cavity, oro-, or hypopharynx or larynx (except T1-2, N0 glottic carcinoma) without distant metastases were randomised to either conventional fractionation (2 Gy/day, 5 days/week in 49 days, total dose 68 Gy) or accelerated fractionation (1.1+2.0 Gy/day, 5 days/week in 35 days, total dose 68 Gy). HRQoL was assessed with EORTC QLQ-C30, QLQ-H&N35 and HADS at baseline, at end of radiotherapy (eRT) and at 3 and 6 months and 1, 2 and 5 years after start of treatment., Results: The AF group reported HRQoL was significantly lower at eRT and at 3 months for most symptoms, scales and functions. Few significant differences were noted between the groups at 6 months and 5 years. Scores related to functional oral intake never reached baseline., Conclusion: In comparison to CF, AF has a stronger adverse effect on HRQoL in the acute phase., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)