Breast Cancer Research and Treatment最新文献

Purpose: To characterize associations of microcalcifications (calcs) with benign breast disease lesion subtypes and assess whether tissue calcs affect risks of ductal carcinoma in situ (DCIS) and invasive breast cancer (IBC).

Methods: We analyzed detailed histopathologic data for 4,819 BBD biopsies from a single institution cohort (2002-2013) followed for DCIS or IBC for a median of 7.4 years for cases (N = 338) and 11.2 years for controls. Natural language processing was used to identify biopsies containing calcs based on pathology reports. Univariable and multivariable regression models were applied to assess associations with BBD lesion type and age-adjusted Cox proportional hazard regressions were performed to model risk of IBC or DCIS stratified by the presence or absence of calcs.

Results: Calcs were identified in 2063 (42.8%) biopsies. Calcs were associated with older age at BBD diagnosis (56.2 versus 49.0 years; P < 0.001). Overall, the risk of developing IBC or DCIS did not differ significantly between patients with calcs (HR 1.13, 95% CI 0.90, 1.41) as compared to patients without calcs. Stratification by BBD severity or subtype, age at BBD biopsy, outcomes of IBC versus DCIS, and mammography technique (screen-film versus full-field digital mammography) did not significantly alter association between calcs and risk.

Conclusion: Our analysis of calcs in BBD biopsies did not find a significant association between calcs and risk of breast cancer.

Purpose: To systematically review the available literature to determine if axillary web syndrome (AWS) is a risk factor for breast cancer-related lymphedema (BCRL) of the upper extremity.

Methods: The study is Prospero-registered (ID CRD42024508169) and follows PRISMA guidelines. Ovid MEDLINE, PubMED, CINAHL, Embase, clinicaltrials.gov and the WHO International Clinical Trials Registry Platform were searched February 24, 2024. Original studies including a cohort of females > 18 years of age diagnosed with AWS after breast cancer surgery and assessing BCRL outcome were included. Scoping, mapping, systematic or qualitative reviews, dissertations without peer-review and conference abstracts were excluded. Methodological quality was assessed using the Modified Downs and Black Checklist and overall certainty in the body of evidence was assessed using Cochrane's GRADE criteria (Grading of Recommendations Assessment, Development and Evaluation).

Results: Nine cohort studies representing 3218 participants were included. The median incidence of AWS and BCRL was 31.79% (IQR 8.90%) and 14.29% (IQR 19.01%), respectively, across all studies. Pooled analysis indicated an odds ratio of 1.19 (95% confidence interval 0.60,2.37), with substantial heterogeneity across studies (Chi² p < 0.0001, I² = 82%). Methodological quality of the included studies was poor to fair, and there was very low certainty evidence indicating no difference in AWS for BCRL risk. The strongest study included, found that AWS more than doubles BCRL risk in the upper extremity.

Conclusion: The available evidence base cannot definitively determine whether AWS imparts risk of BCRL. AWS should be considered a potential risk factor for BCRL, until definitive conclusions from future research are available.

Purpose: To evaluate the prevalence and characteristics of different HER2 categories among patients with advanced breast cancer (aBC) and describe treatment patterns and outcomes of those with HER2-low disease.

Methods: A retrospective cohort study was conducted via chart review at the Huntsman Cancer Institute, including patients diagnosed with aBC (stages IIIB, IIIC and IV) between 2010 and 2019. All patients with IHC1+ were considered HER2-low unless FISH was positive. Patients with IHC2+ were only classified as HER2-low if a negative FISH was documented. The prevalence and characteristics of each HER2 category were reported. Treatment patterns and survival outcomes of HER2-low patients who received first line treatment in 2017 or later were presented.

Results: A total of 240 of 414 patients (58%) with aBC were HER2-low, with the majority of patients (83%) classified as hormone receptor (HR)-positive. In first line, most HR-positive patients received endocrine therapy with chemotherapy for stage IIIB/IIIC (47%) and with CDK4/6 inhibitors for stage IV breast cancer (50%) Most HR-negative patients received chemotherapy alone (92% for stage IIIB/IIIC, 60% for stage IV). In second line, chemotherapy alone was the most common modality (21.4% for HR-positive; 45.5% for HR-negative). Median overall survival was 37.7 months while median progression-free survival from first line was 18.0 months, decreasing to 8.0 months in second line.

Conclusion: A substantial proportion of patients previously classified as HER2-negative have low but detectable HER2 expression and may benefit from novel HER2-directed agents, which have demonstrated clinical benefit in this population post-chemotherapy.

Purpose: While cancer phenotypes in carriers of a single mutant allele in most major cancer susceptibility genes are well-established, there is a paucity of data on the phenotype of carriers of two pathogenic variants-double heterozygotes (DH) or homozygous carriers. Here, we describe the phenotype of carriers of homozygous and DH pathogenic sequence variants (PSVs) in major cancer susceptibility genes.

Methods: Individuals referred for multigene panel testing at Blueprint Genetics laboratory were included. Ethically approved comparison of cancer type and age at diagnosis between DH, homozygous, and single PSV carriers was performed per gene.

Results: Of 6,685 eligible participants, 928 (13.9%) were single heterozygous PSV carriers, 6 (0.09%) were homozygous PSV carriers, and 17 (0.25%) were DH PSV carriers. Mean age at diagnosis of any cancer among single PSV age was 46.8 ± 14.9 years and among DH PSV carriers 37.6 ± 13.0 years (P < 0.0001). Notably, age at diagnosis for breast cancer among single BRCA1 PSV carriers (n = 59) was 43.8 ± 8.7 years (p = 0.7606), among single BRCA2 PSV carriers (n = 52)-47.9 ± 13.0 years (p = 0.2274) compared with 42.3 ± 13.0 years among DH PSV carriers (n = 10- 9 of whom were carriers of either BRCA1 or BRCA2).

Conclusion: DH for PSV in two cancer susceptibility genes is a rare event, and the mean age at cancer diagnosis is younger in DH PSV carriers compared with single PSV carriers.

Purpose: Late alopecia, defined as incomplete hair regrowth > 6 months following cytotoxic chemotherapy or > 6 months from initiation of endocrine therapy, negatively impacts quality of life and may affect dose intensity of adjuvant therapy. This study investigates the effect of oral minoxidil in women with chemotherapy and/or endocrine therapy-induced late alopecia.

Methods: The rate of clinical response was assessed by standardized photography and quantitated with trichoscopy.

Results: Two hundred and sixteen patients (mean age 57.8 ± 13.7) were included. The most common cancer diagnosis was breast, in 170 patients (79.1%). Alopecia developed after chemotherapy in 31 (14.4%) patients, endocrine monotherapy in 65 (30.1%) patients, and chemotherapy followed by endocrine therapy in 120 (55.6%) patients. In 119 patients, standardized photography assessments were used to determine clinical change in alopecia after a median of 105 (IQR = 70) days on oral minoxidil and revealed improvement in 88 (74%) patients. Forty-two patients received quantitative trichoscopic assessments at baseline and at follow-up after a median of 91 (IQR = 126) days on oral minoxidil. Patients had clinically and statistically significant increases in frontal hair shaft density (from 124.2 hairs/cm² at initial to 153.2 hairs/cm² at follow-up assessment, p = 0.008) and occipital shaft density (from 100.3 hairs/cm² at initial to 123.5 hairs/cm² at follow-up assessment. p = 0.004). No patients discontinued oral minoxidil due to adverse events.

Conclusions: Overall, oral minoxidil was well tolerated by patients and may benefit both frontal and occipital late alopecia in cancer survivors treated with cytotoxic and/or endocrine therapy by increasing hair shaft and follicle density.

Introduction: Homologous recombination (HR) is a crucial DNA-repair mechanism, and its disruption can lead to the accumulation of mutations that initiate and promote cancer formation. The key HR genes, BRCA1 and BRCA2, are particularly significant as their germline pathogenic variants are associated with a hereditary predisposition to breast and/or ovarian cancer.

Materials and methods: The study was performed on 45 FFPE breast cancer tissues obtained from 24 and 21 patients, with and without the germline BRCA1/2 mutation, respectively. The expression of 11 genes: BRCA1, BRCA2, ATM, BARD1, FANCA, FANCB, FANCI, RAD50, RAD51D, BRIP1, and CHEK2 was assessed using Custom RT2 PCR Array (Qiagen), and results were analysed using R.

Results: Cancer tissues from patients with BRCA1 or BRCA2 germline mutations displayed no significant differences in the expression of the selected HR genes compared to BRCA1 or BRCA2 wild-type cancer tissues. In BRCA1^mut cancer tissues, BRCA1 expression was significantly higher than in BRCA2^mut and BRCA wild-type cancer tissues.

Conclusions: In cancer tissues harbouring either BRCA1 or BRCA2 germline mutations, no significant differences in expression were observed at the mRNA level of any tested HR genes, except BRCA1. However, the significant differences observed in BRCA1 expression between germline BRCA1^mut, germline BRCA2^mut and BRCA1/2^wt tissues may indicate a compensatory mechanism at the mRNA level to mitigate the loss of BRCA1 function in the cells.

Purpose: Aromatase inhibitors (AI) block estrogen synthesis and are used as long-term adjuvant treatment for breast cancer in postmenopausal women. AI use can be associated with weight gain that can lead to increased cardiometabolic risk. The response to anti-obesity medications (AOM) in patients using AI has yet to be studied. We sought to investigate weight loss outcomes of AOM in patients taking AI for breast cancer treatment.

Methods: This is a matched retrospective cohort study of breast cancer survivors on AI using AOM (AOM/AI group). We compared their weight loss outcomes with a group of female patients with obesity, without a history of breast cancer or AI use, on AOM (AOM group). The primary endpoint was total body weight loss percentage (TBWL %) at the last follow-up. We performed mixed linear regression models, including diabetes status at baseline, to assess associations between use of AOM with/without AI with total body weight loss percentage (TBWL%).

Results: We included 124 patients: 62 in the AOM/AI group (63.6 ± 10 years, body mass index [BMI] 34.3 ± 7.1 kg/m²) and 62 in the AOM group (62.8 ± 9.9 years, BMI 34.6 ± 6.5 kg/m²). The mean time of follow up was 9.3 ± 3.5 months, with no differences among the two groups. The AOM/AI group had a lower TBWL% compared to the AOM group at the last follow-up -5.3 ± 5.0 vs. -8.2 ± 6.3 (p = 0.005). The results remained significant after adjusting for diabetes status (p = 0.0002). At 12 months, the AOM/AI group had a lower TBWL% compared to the AOM group 6.4 ± 0.8% vs. 9.8 ± 0.9% (p = 0.04). The percentage of patients achieving ≥ 5%, ≥ 10%, and ≥ 15% of weight loss at 12 months was greater in the AOM compared to the AOM/AI group. Although the weight loss response was suboptimal, patients in the AOM/AI group had improvement in fasting glucose, glycated hemoglobin, systolic blood pressure, and low-density lipoprotein cholesterol.

Conclusions: The use of AI in breast cancer survivors is associated with less weight loss response to AOM compared to patients without breast cancer history and who do not take AI. Studies are needed to assess the mechanisms behind the differential weight loss response to AOM in women taking AI.

Purpose: Patients with invasive lobular carcinoma (ILC) face high rates of positive margins and completion mastectomy, which can be improved with the use of specific techniques, such as oncoplastic surgery. However, prior studies have shown that type of breast cancer surgery performed is also associated with patient factors such as elevated body mass index (BMI). Thus, this study investigates whether BMI impacts the type of surgical interventions in patients with ILC.

Methods: A retrospective analysis of 705 patients with stage I-III ILC from an institutional database was conducted. Patients were stratified by BMI (underweight, normal weight, overweight, obese). Pearson's Chi-square, ANOVA, and multivariable logistic regression were used to evaluate the relationship between BMI and surgical procedures.

Results: Breast-conserving surgery (BCS) was the initial operation in 60% of patients, with no significant difference by BMI. Among those undergoing BCS, patients with obese BMI were significantly more likely to undergo oncoplastic surgery (46.9% vs. 7.7%, 37.3%, and 33.6% for underweight, normal, and overweight, respectively, p = 0.032). Obese BMI patients undergoing mastectomy were less likely to have reconstruction compared to those with underweight, normal weight, and overweight BMI (44.2% vs. 50%, 71.1%, and 64.1%, p = 0.002).

Conclusion: Overweight/obese BMI patients with ILC underwent different surgical interventions compared to those with lower BMI. While initial BCS rates were similar, overweight/obese patients had higher oncoplastic surgery rates in BCS and lower reconstruction rates in mastectomy. Further research is needed to understand BMI's impact on surgical decisions and outcomes in ILC.