Quantitative Multiparametric MRI as an Imaging Biomarker for the Prediction of Breast Cancer Receptor Status and Molecular Subtypes

ObjectivesTo assess breast cancer receptor status and molecular subtypes by using the CAIPIRINHA-Dixon-TWIST-VIBE and readout-segmented echo-planar diffusion weighted imaging techniques.MethodsA total of 165 breast cancer patients were retrospectively recruited. Patient age, estrogen receptor, progesterone receptor, human epidermal growth factorreceptor-2 (HER-2) status, and the Ki-67 proliferation index were collected for analysis. Quantitative parameters (Ktrans, Ve, Kep), semiquantitative parameters (W-in, W-out, TTP), and apparent diffusion coefficient (ADC) values were compared in relation to breast cancer receptor status and molecular subtypes. Statistical analysis were performed to compare the parameters in the receptor status and molecular subtype groups.Multivariate analysis was performed to explore confounder-adjusted associations, and receiver operating characteristic curve analysis was used to assess the classification performance and calculate thresholds.ResultsYounger age (<49.5 years, odds ratio (OR) =0.95, P=0.004), lower Kep (<0.704,OR=0.14, P=0.044),and higher TTP (>0.629 min, OR=24.65, P=0.011) were independently associated with progesterone receptor positivity. A higher TTP (>0.585 min, OR=28.19, P=0.01) was independently associated with estrogen receptor positivity. Higher Kep (>0.892, OR=11.6, P=0.047), lower TTP (<0.582 min, OR<0.001, P=0.004), and lower ADC (<0.719 ×10-3 mm2/s, OR<0.001, P=0.048) had stronger independent associations with triple-negative breast cancer (TNBC) compared to luminal A, and those parameters could differentiate TNBC from luminal A with the highest AUC of 0.811.ConclusionsKep and TTP were independently associated with hormone receptor status. In addition, the Kep, TTP, and ADC values had stronger independent associations with TNBC than with luminal A and could be used as imaging biomarkers for differentiate TNBC from Luminal A.

Safety of hormone replacement therapy in women with a history of cervical adenocarcinoma

Objectives Studies investigating the safety of hormone replacement therapy in cervical cancer have predominantly included patients with squamous disease. Pathological studies have identified estrogen receptor positivity in cervical adenocarcinomas. A recent small case-control study suggested a trend towards reduced survival with hormone replacement therapy in cervical adenocarcinomas. Our objective was to determine if hormone replacement therapy use in patients treated for cervical adenocarcinomas is detrimental to survival. Study design A retrospective review of all women under the age of 50 with stage 1B-2B cervical adenocarcinomas diagnosed between 1 November 2000 and 24 September 2019. Women were categorised into three groups: ovaries conserved (OVCON); or iatrogenic menopause with (IM-HRT) or without (IM-NOHRT) hormone replacement therapy. Hormone replacement therapy use was defined on an intention to treat basis. Statistical analysis was performed using Kaplan-Meier and Cox proportional hazards methods. Main outcome measures Overall (OS), disease specific (DSS) and progression free (PFS) survival. Results A total of 58 women (mean age 38.5 ± 6.6) were included in the study of whom 25 (43.1%) had OVCON, 20 (34.4%) had IM-HRT and 13 (22.4%) had IM-NOHRT. No menopause-associated deaths occurred. Although five-year DSS was 73% in IM-NOHRT compared to 95% in IM-HRT and 95% in OVCON, these differences were not statistically significant. Five-year PFS was 68% in IM-NOHRT compared to 90% in IM-HRT and 81% in OVCON but again, these differences were not statistically significant. Conclusion In this small study, hormone replacement therapy does not appear to be detrimental to survival in cervical adenocarcinomas. There is a trend towards improved survival with hormone replacement therapy. Larger studies are required to substantiate these findings.

Lymph Node Involvement and Related Risk Factors in Patients With Breast Cancer Referred for Radiotherapy: A 20-Year Study on 15000 Women

Objectives: Tumor size and axillary lymph node (LN) involvement are used as prognostic markers and a guide for choosing adjuvant therapy. This study aimed to evaluate LN involvement and related risk factors in patients with breast cancer (BC) referred for radiotherapy. Materials and Methods: Using the census sampling method, 15,000 women with BC referring for radiotherapy were enrolled in this retrospective descriptive study performed at Tabriz University of Medical Sciences during 2000-2020. LN involvement and related risk factors were recorded and analyzed using the t test and ANOVA test at a significance level of P<0.05. Results: The prevalence of LN involvement in this study was 25%. The estrogen receptor status and LN involvement were associated with metastasis. The odds ratio of metastasis in patients with a negative estrogen receptor was about twice that of women with estrogen receptor positivity. Finally, the risk of metastasis in patients presenting with LN involvement was eight times higher than that of patients without LN involvement. Conclusion: In general, estrogen receptor status and LN involvement were associated with metastasis in patients with BC. Thus, these factors can be regarded as a guide to start necessary interventions earlier in at-risk patients.

Does Concomitant DCIS Affect the Clinical Outcome in Breast Cancer Patients with Invasive Ductal Carcinoma: an Asian Perspective

BackgroundDuctal carcinoma in situ (DCIS) is an established precursor to invasive ductal carcinoma (IDC) and its coexistence with IDC appear to favour reduced biological aggressiveness. Its prognostic implication and ability to affect clinical outcome has been understudied in Asia. This study aims to explore if concomitant DCIS affects the clinical behavior and outcomes among Asians. MethodsStage I to III breast cancer patients with histologically proven invasive ductal carcinoma, diagnosed and treated in a single institution from 1 June 2004 to 30 June 2014 were included in this study. Statistical analyses were conducted using x2 test, independent T- test, multi-variate logistic regression and Kaplan- Meier test.ResultsA total of 818 patients were identified, including 224 and 594 patients with isolated IDC (No-DCIS) and IDC with coexisting DCIS (IDC-DCIS) respectively. Patients with IDC-DCIS were found to have smaller tumours (median: 22mm, p<=0.01), estrogen receptor positivity (p=0.001), progesterone receptor positivity (p<0.001) and associated with better pathological stage (p=0.001). Patients with No-DCIS were 1.6 times more likely to develop disease progression (95% CI: 1.1- 2.3, p=0.027) and subsequently associated with distant recurrences (20.5% vs 13.6%, p=0.02). The breast cancer specific 5 year overall survival rate for patients with No-DCIS and those with IDC-DCIS was 90.9% (95% CI: 86.2% - 94.5%) and 93.7% (95% CI: 91.4- 95.5%) respectively (p=0.202).ConclusionThe presence of DCIS component in IDC among Asians is associated with favourable tumour biological profile, thereby indicating reduced disease aggressiveness. Our study is the first to report the clinical significance in terms of disease progression and distant recurrences among Asians. Trial registrationThis study had received the approval of the institutional ethics committee prior to its commencement (IRB Ref No: 2019/2884).

Lobular Breast Cancer: A Review

Invasive lobular carcinoma accounts for 5%–15% of all invasive breast cancers, with a marked increase in incidence rates over the past two decades. Distinctive biological hallmarks of invasive lobular carcinoma include the loss of cell adhesion molecule E-cadherin leading to cells with a discohesive morphology, proliferating into single-file strands and estrogen receptor positivity. These key molecular features can make diagnosis difficult, as invasive lobular carcinoma is challenging to detect both physically and with current standard imaging. Treatment of invasive lobular carcinoma strongly favors endocrine therapy due to low chemosensitivity and lower rates of pathological response as a result. This review will summarize the distinct biological and molecular features of invasive lobular carcinoma, focusing on the diagnostic challenges faced and the subsequent surgical and medical management strategies. Prospective therapeutic options will also be explored, highlighting how furthering our understanding of the unique biology of lobular breast carcinoma is essential in guiding and informing the treatment of patients in the future.

Radiological review of prior screening mammograms of screen-detected breast cancer

Objective To perform a radiological review of mammograms from prior screening and diagnosis of screen-detected breast cancer in BreastScreen Norway, a population-based screening program. Methods We performed a consensus-based informed review of mammograms from prior screening and diagnosis for screen-detected breast cancers. Mammographic density and findings on screening and diagnostic mammograms were classified according to the Breast Imaging-Reporting and Data System®. Cases were classified based on visible findings on prior screening mammograms as true (no findings), missed (obvious findings), minimal signs (minor/non-specific findings), or occult (no findings at diagnosis). Histopathologic tumor characteristics were extracted from the Cancer Registry of Norway. The Bonferroni correction was used to adjust for multiple testing; p < 0.001 was considered statistically significant. Results The study included mammograms for 1225 women with screen-detected breast cancer. Mean age was 62 years ± 5 (SD); 46% (567/1225) were classified as true, 22% (266/1225) as missed, and 32% (392/1225) as minimal signs. No difference in mammographic density was observed between the classification categories. At diagnosis, 59% (336/567) of true and 70% (185/266) of missed cancers were classified as masses (p = 0.004). The percentage of histological grade 3 cancers was higher for true (30% (138/469)) than for missed (14% (33/234)) cancers (p < 0.001). Estrogen receptor positivity was observed in 86% (387/469) of true and 95% (215/234) of missed (p < 0.001) cancers. Conclusions We classified 22% of the screen-detected cancers as missed based on a review of prior screening mammograms with diagnostic images available. One main goal of the study was quality improvement of radiologists’ performance and the program. Visible findings on prior screening mammograms were not necessarily indicative of screening failure. Key Points • After a consensus-based informed review, 46% of screen-detected breast cancers were classified as true, 22% as missed, and 32% as minimal signs. • Less favorable prognostic and predictive tumor characteristics were observed in true screen-detected breast cancer compared with missed. • The most frequent mammographic finding for all classification categories at the time of diagnosis was mass, while the most frequent mammographic finding on prior screening mammograms was a mass for missed cancers and asymmetry for minimal signs.

Correlation of histological grade with Estrogen, Progesterone and HER2/neu reactivity in breast cancer

Background: Treatment modalities and prognosis of breast carcinoma depend largely on their hormone receptors (Estrogen and Progesterone Receptors) and HER2/neu profile. Various studies conducted within Nepal have highlighted their overall status in breast carcinomas but studies on their correlation with histological grade are few. This study aims to correlate hormone receptors and HER2/neu status with different histological grades of invasive breast carcinoma. Materials and Methods: This is a retrospective analysis of cases received at Intrepid Cancer Diagnostics, Nepal between January 2015 to December 2018 for evaluation of status of hormonal receptors and HER2/ neu on invasive breast carcinomas. Mastectomy and excisional biopsies were included for statistical correlation between hormone receptors, HER2/neu and histological grades (n=364). P-value<=0.01 was considered statistically significant. Results: Of 364 invasive carcinomas categorized into grades 1, 2 and 3, Estrogen Receptor positivity was noted in 77.3% (34/44), 60.8% (115/189) and 28.2% (37/131) respectively; Progesterone Receptor positivity was noted in 61.4% (27/44), 52.4% (99/189) and 21.4% (28/131) respectively; HER2/neu positivity was noted in 18.2% (8/44), 20.1% (38/189) and 19.8% (26/131) respectively. Triple negativity was found to be 9.1% (4/44), 21.7% (41/189) and 41.9% (55/131) in grade 1, 2 and 3 carcinomas respectively. Conclusions: Estrogen and Progesterone receptor expressing carcinomas were found to be more often of grade 1 category, with this rate declining through grades 2 and 3. No such correlation was noted for HER2/neu. Triple negative carcinomas were found to be of higher grade (grade 3).

Contrasting Epidemiology and Clinicopathology of Female Breast Cancer in Asians vs the US Population

Background The incidence of breast cancer among younger East Asian women has been increasing rapidly over recent decades. This international collaborative study systemically compared the differences in age-specific incidences and pathological characteristics of breast cancer in East Asian women and women of predominantly European ancestry. Methods We excerpted analytic data from six national cancer registries (979 675 cases) and eight hospitals (18 008 cases) in East Asian countries and/or regions and, for comparisons, from the US Surveillance, Epidemiology, and End Results program database. Linear regression analyses of age-specific incidences of female breast cancer and logistic regression analyses of age-specific pathological characteristics of breast cancer were performed. All statistical tests were two-sided. Results Unlike female colorectal cancer, the age-specific incidences of breast cancer among East Asian women aged 59 years and younger increased disproportionally over recent decades relative to rates in US contemporaries. For years 2010–2014, the estimated age-specific probability of estrogen receptor positivity increased with age in American patients, whereas that of triple-negative breast cancer (TNBC) declined with age. No similar trends were evident in East Asian patients; their probability of estrogen receptor positivity at age 40–49 years was statistically significantly higher (odd ratio [OR] = 1.50, 95% confidence interval [CI] = 1.36 to 1.67, P &lt; .001) and of TNBC was statistically significantly lower (OR = 0.79, 95% CI = 0.71 to 0.88, P &lt; .001), whereas the probability of ER positivity at age 50–59 years was statistically significantly lower (OR = 0.88, 95% CI = 0.828 to 0.95, P &lt; .001). Subgroup analyses of US Surveillance, Epidemiology, and End Results data showed similarly distinct patterns between East Asian American and white American patients. Conclusions Contrasting age-specific incidences and pathological characteristics of breast cancer between East Asian and American women, as well as between East Asian Americans and white Americans, suggests racial differences in the biology.