Hotspot mutations have been identified with cancer hotspot database ( http://cancerhotspots.org) 26, 75 using protein change annotation retrieved from TransVar 73. The mammary gland’s appearance is subject to changes due to age, weight variation, physical activity, and concomitant ailments (Poland’s syndrome, Breast Cancer, etc.), as well as hormone exposure during puberty, pregnancy, breast feeding and menopause [3]. Because of the variability of this organ, a great amount of skill is needed to plan and predict the results of any procedure. Rosenthal, R., McGranahan, N., Herrero, J., Taylor, B. S. & Swanton, C. DeconstructSigs: delineating mutational processes in single tumors distinguishes DNA repair deficiencies and patterns of carcinoma evolution. Genome Biol. 17, 31 (2016). Banerji, S. et al. Sequence analysis of mutations and translocations across breast cancer subtypes. Nature 486, 405–409 (2012).

breast (58.9/41.1), Left breast (58.9/41.0). Then expressed by decade of life were: 3rd decade of life (57.8:42.1), Fourth decade of life (59.6:40.3), Fifth decade of life (57.9:42), >6 th decade of life (61.5:38.4). And for the left breast were: 3rd decade of life (57.7:42.2), Fourth decade of life (59.2:40.7), Fifth decade of life (58.3:41.6), >6 th decade of life (62.1:37.8) ( Figure 8). Villarreal-Garza, C. et al. Real-world outcomes in young women with breast cancer treated with neoadjuvant chemotherapy. Breast Cancer Res. Treat. 157, 385–394 (2016). Hatakeyama, K. et al. Mutational burden and signatures in 4000 Japanese cancers provide insights into tumorigenesis and response to therapy. Cancer Sci. 110, 2620–2628 (2019). Oncogenic networks with mutually exclusive genomic alterations between somatic-mutations and SCNA were identified through MEMo algorithm 29 in the profiled HM patients. Two significantly modules (adjusted p< 0.1), affecting a considerable proportion of samples were detected (Fig. 7d, e). Notably, ERBB2 ( HER2) amplification tend to exclude PIK3CA/AKT1 mutations (Fig. 7e). Of relevance, HER2 amplification is highly correlated with its expression ( R = 90%, adj p-value < 0.05, Fig. 7c) and might be able to activate PI3K/AKT signaling in a HER3 independent mechanism 30, suggesting that redundant alterations over the same pathway leads to a disadvantage for the cell. Likewise, PIK3CA, AKT1 and CDH1 gain-of-function mutations were mutually exclusive. Similarly, TP53 inactivation was mutually exclusive with PIK3CA/AKT1 mutations in most of the altered cases, nonetheless we found a 15% of co-occurrence (Fig. 7d, e). The oncogenic amplification of CCND1, a cell cycle regulatory molecule, was mutually exclusive with TP53 mutation. Interestingly, amplification of CCND1 is also correlated with its over-expression (R = 40%, adj p-value < 0.05, Fig. 7c) and consequently enhance G1-S progression through RB/E2F 31. The observed mutual exclusivity among diverse alterations in TP53 tumor suppressor pathways indicates different manners to dismantle cell division 32. Although a small proportion of CCND1 amplified tumors co-occurred with HER2 amplification (3/12) and PIK3CA mutations (4/12), they were generally mutually excluded. Of interest, in addition to CCND1 amplification, CCND1 can be up-regulated through other mechanisms such as ERBB2 driven-activation or by the PI3K-AKT-mTOR pathway, suggesting a functional redundancy of these alterations, and more than one of these alterations might be disadvantageous for the tumoral cell (Fig. 7d, e and Supplementary Data 9). These results pointed out the relevance of PI3K/AKT and ERBB2 signaling pathways alterations as key tumorigenic events, suggesting that these multiple alterations should be considered prior to determining therapy based on molecular characterization. Immune infiltration characterization of breast tumors along ancestriesForbes, S. A. et al. COSMIC: mining complete cancer genomes in the Catalogue of Somatic Mutations in Cancer. Nucleic Acids Res. 39, D945–D950 (2011).

Moreover, we identified recurrent alterations that particularly affect HM tumor genomes, such as the enrichment of AKT1 E17K mutation in HR + tumors, with a prevalence of 8%. Interestingly, although this amino acid alteration was identified as a recurrent hotspot mutation in BC 26, 41, other profiles report a lower frequency, ranging from 1.4% to 5.9% in different ancestries 42, 43, 44, with a mean frequency of 3.8%. In accordance with these data, through our in-silico analysis of large-scale sequencing studies, we were only able to detect a similar frequency in young BC patients (<35 years) from South Korea, with 8% (4/50), but not in any other dataset of tumors analyzed, nor this has been previously reported by other study, to the best of our knowledge. Cibulskis, K. et al. Sensitive detection of somatic point mutations in impure and heterogeneous cancer samples. Nat. Biotechnol. 31, 213–219 (2013). Whole-exome was captured through Agilent SureSelect ExomePlus bait system (Agilent Technologies, USA) and biotinylated RNA baits 67 process. ~155 Mb baits were target including the standard exome, plus intronic and promoter sequences for known cancer genes, relevant targets identified by cancer genomic studies, TCGA and the Cancer Cell Line Encyclopedia. Exome libraries were sequenced on Illumina GAII or HiSeq 2000 (Illumina, USA) sequencers with 76 base-paired-end reads achieving a mean of 141x. Alignment was performed with the Burrows–Wheeler Alignment tool 68 and standard Picard pipeline to the human genome assembly hg19/GRCh37. Somatic mutation analysisThis study evaluates the mean values of breast anthropometric measurements in a sample of Healthy Mexican Female volunteers, with the objective of establishing reference values for our patient population. Adequate proportions play an important role in the aesthetic aspect of the breast, therefore a proper analysis and planning must be done for surgeons to obtain better results. In recent times, style icon, beauty mogul, and new mom Rihanna is lensed with her curves in focus for the September 2020 cover story. Other famous faces include Goop mogul Gwyneth Paltrow, the always-stunning Jennifer Aniston, as well as burgeoning supermodel, runway fixture, and J6 brand muse Anok Yai—who was featured in a sexy suiting story months earlier. Hailey Bieber, Demi Lovato, and everyone's favorite modeling duo Bella and Gigi Hadid are also on the list. Curtis, C. et al. The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups. Nature 486, 346–352 (2012). Laboratorio de Biología Computacional, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico

Rheinbay, E. et al. Recurrent and functional regulatory mutations in breast cancer. Nature 547, 55–60 (2017). Genomics Laboratory, Red de Apoyo a la Investigación, Universidad Nacional Autónoma de México-Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México City, MéxicoBig breasts might seem like a blessing to some. However, one buxom influencer finds her cumbersome chest to be a massive burden, as she’s allegedly forced to wear multiple bras at once to work out, among other inconveniences. The blond bombshell showed off her apparently problematic mammaries in a series of TikTok videos with millions of views. Kim, S. B. et al. Ipatasertib plus paclitaxel versus placebo plus paclitaxel as first-line therapy for metastatic triple-negative breast cancer (LOTUS): a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Oncol. 18, 1360–1372 (2017).