bims-eabrec 2023-02-19 papers

Issue of 2023–02–19
four papers selected by
Rakesh Kumar, Swami Rama University

Breast. 2023 Feb 08. pii: S0960-9776(23)00027-9. [Epub ahead of print]68 163-172

Early breast cancer in women aged 35 years or younger: A large national multicenter French population-based case control-matched analysis.

Ondine Dufour, Gilles Houvenaeghel, Jean-Marc Classe, Monique Cohen, Christelle Faure, Chafika Mazouni, Marie-Pierre Chauvet, Eva Jouve, Emile Darai, Anne-Sophie Azuar, Pierre Gimbergues, Anthony Gonçalves, Alexandre de Nonneville.

BACKGROUND: There is a scarcity of data exploring early breast cancer (eBC) in very young patients. We assessed shared and intrinsic prognostic factors in a large cohort of patients aged ≤35, compared to a control group aged 36 to 50.
METHODS: Patients ≤50 were retrospectively identified from a multicentric cohort of 23,134 eBC patients who underwent primary surgery between 1990 and 2014. Multivariate Cox analyses for DFS and OS were built. To assess the independent impact of age, 1 to 3 case-control analysis was performed by matching ≤35 and 36-50 years patients.
RESULTS: Of 6481 patients, 556 were aged ≤35, and 5925 from 36 to 50. Age ≤35 was associated with larger tumors, higher grade, ER-negativity, macroscopic lymph node involvement (pN + macro), lymphovascular invasion (LVI), mastectomy, and chemotherapy (CT) use. In multivariate analysis, age ≤35 was associated with worse DFS [HR 1.56, 95% CI 1.32-1.84; p < 0.001], and OS [HR 1.29, 95% CI 1.03-1.60; p = 0.025], as were high grade, large tumor, LVI, pN + macro, ER-negativity, period of diagnostic, and absence of ET or CT (for DFS). Adverse prognostic impact of age ≤35 was maintained in the case control-matched analysis for DFS [HR 1.56, 95%CI 1.28-1.91, p < 0.001], and OS [HR 1.33, 95%CI 1.02-1.73, p = 0.032]. When only considering patients ≤35, ER, tumor size, nodal status, and LVI were independently associated with survival in this subgroup.
CONCLUSIONS: Age ≤35 is associated with less favorable presentation and more aggressive treatment strategies. Our results support the poor prognosis value of young age, which independently persisted when adjusting for other prognostic factors and treatments.

Keywords: Early breast cancer; Impact of age; Prognostic of young age; Under 35 years old; Very young patient; Young breast cancer

DOI: https://doi.org/10.1016/j.breast.2023.02.004

Cancer Epidemiol Biomarkers Prev. 2023 Feb 10. pii: EPI-22-0405. [Epub ahead of print]

Application of novel breast biospecimen cell type adjustment identifies shared DNA methylation alterations in breast tissue and milk with breast cancer risk factors.

Meghan E Muse, Connolly D Carroll, Lucas A Salas, Margaret R Karagas, Brock C Christensen.

BACKGROUND: DNA methylation patterning is cell-type-specific and altered DNA methylation is well established to occur early in breast carcinogenesis, affecting non-cancerous, histopathologically normal breast tissue. Previous work assessing risk factor-associated alterations to DNA methylation in breast tissue has been limited, with even less published research in breast milk, a non-invasively obtained biospecimen containing sloughed mammary epithelial cells that may identify early alterations indicative of cancer risk.
METHODS: Here, we present a novel library for the estimation of the cellular composition of breast tissue and milk and subsequent assessment of cell type-independent alterations to DNA methylation associated with established breast cancer risk factors in solid breast tissue (n = 95) and breast milk (n = 48) samples using genome-scale DNA methylation measures from the Illumina HumanMethylation450 array.
RESULTS: We identified 772 hypermethylated CpGs (P < 0.01) associated with age consistent between breast tissue and breast milk samples. Age-associated hypermethylated CpG loci were significantly enriched for CpG island shore regions known to be important for regulating gene expression. Among the overlapping hypermethylated loci mapping to genes, a differentially methylated region was identified in the promoter region of SFRP2, a gene observed to undergo promoter hypermethylation in breast cancer.
CONCLUSIONS: Our findings suggest the potential to identify epigenetic biomarkers of breast cancer risk in noninvasively obtained, tissue-specific breast milk specimens.
IMPACT: This work demonstrates the potential of using breast milk as a non-invasive biomarker of breast cancer risk, improving our ability to detect early stage disease and lowering the overall disease burden.

DOI: https://doi.org/10.1158/1055-9965.EPI-22-0405

N Engl J Med. 2023 Feb 16. 388(7): 585-594

Breast-Conserving Surgery with or without Irradiation in Early Breast Cancer.

Ian H Kunkler, Linda J Williams, Wilma J L Jack, David A Cameron, J Michael Dixon.

BACKGROUND: Limited level 1 evidence is available on the omission of radiotherapy after breast-conserving surgery in older women with hormone receptor-positive early breast cancer receiving adjuvant endocrine therapy.
METHODS: We performed a phase 3 randomized trial of the omission of irradiation; the trial population included women 65 years of age or older who had hormone receptor-positive, node-negative, T1 or T2 primary breast cancer (with tumors ≤3 cm in the largest dimension) treated with breast-conserving surgery with clear excision margins and adjuvant endocrine therapy. Patients were randomly assigned to receive whole-breast irradiation (40 to 50 Gy) or no irradiation. The primary end point was local breast cancer recurrence. Regional recurrence, breast cancer-specific survival, distant recurrence as the first event, and overall survival were also assessed.
RESULTS: A total of 1326 women were enrolled; 658 were randomly assigned to receive whole-breast irradiation and 668 to receive no irradiation. The median follow-up was 9.1 years. The cumulative incidence of local breast cancer recurrence within 10 years was 9.5% (95% confidence interval [CI], 6.8 to 12.3) in the no-radiotherapy group and 0.9% (95% CI, 0.1 to 1.7) in the radiotherapy group (hazard ratio, 10.4; 95% CI, 4.1 to 26.1; P<0.001). Although local recurrence was more common in the group that did not receive radiotherapy, the 10-year incidence of distant recurrence as the first event was not higher in the no-radiotherapy group than in the radiotherapy group, at 1.6% (95% CI, 0.4 to 2.8) and 3.0% (95% CI, 1.4 to 4.5), respectively. Overall survival at 10 years was almost identical in the two groups, at 80.8% (95% CI, 77.2 to 84.3) with no radiotherapy and 80.7% (95% CI, 76.9 to 84.3) with radiotherapy. The incidence of regional recurrence and breast cancer-specific survival also did not differ substantially between the two groups.
CONCLUSIONS: Omission of radiotherapy was associated with an increased incidence of local recurrence but had no detrimental effect on distant recurrence as the first event or overall survival among women 65 years of age or older with low-risk, hormone receptor-positive early breast cancer. (Funded by the Chief Scientist Office of the Scottish Government and the Breast Cancer Institute, Western General Hospital, Edinburgh; ISRCTN number, ISRCTN95889329.).

DOI: https://doi.org/10.1056/NEJMoa2207586

Breast Cancer Res Treat. 2023 Feb 17.

Changes in mammographic density and risk of breast cancer among a diverse cohort of women undergoing mammography screening.

Aimilia Gastounioti, Eric A Cohen, Lauren Pantalone, Sarah Ehsan, Sanjana Vasudevan, Avinash Kurudi, Emily F Conant, Jinbo Chen, Despina Kontos, Anne Marie McCarthy.

PURPOSE: Mammographic density (MD) is a strong breast cancer risk factor. MD may change over time, with potential implications for breast cancer risk. Few studies have assessed associations between MD change and breast cancer in racially diverse populations. We investigated the relationships between MD and MD change over time and breast cancer risk in a large, diverse screening cohort.
MATERIALS AND METHODS: We retrospectively analyzed data from 8462 women who underwent ≥ 2 screening mammograms from Sept. 2010 to Jan. 2015 (N = 20,766 exams); 185 breast cancers were diagnosed 1-7 years after screening. Breast percent density (PD) and dense area (DA) were estimated from raw digital mammograms (Hologic Inc.) using LIBRA (v1.0.4). For each MD measure, we modeled breast density change between two sequential visits as a function of demographic and risk covariates. We used Cox regression to examine whether varying degrees of breast density change were associated with breast cancer risk, accounting for multiple exams per woman.
RESULTS: PD at any screen was significantly associated with breast cancer risk (hazard ratio (HR) for PD = 1.03 (95% CI [1.01, 1.05], p < 0.0005), but neither change in breast density nor more extreme than expected changes in breast density were associated with breast cancer risk. We found no evidence of differences in density change or breast cancer risk due to density change by race. Results using DA were essentially identical.
CONCLUSIONS: Using a large racially diverse cohort, we found no evidence of association between short-term change in MD and risk of breast cancer, suggesting that short-term MD change is not a strong predictor for risk.

Keywords: Breast cancer; Breast density; Cancer screening; Mammography

DOI: https://doi.org/10.1007/s10549-023-06879-2