Association between Breast Cancer Polygenic Risk Score and Chemotherapy-Induced Febrile Neutropenia: Null Results.

BACKGROUND: The hypothesis that breast cancer (BC) susceptibility variants are linked to chemotherapy-induced toxicity has been previously explored. Here, we investigated the association between a validated 313-marker-based BC polygenic risk score (PRS) and chemotherapy-induced neutropenia without fever and febrile neutropenia (FNc) in Asian BC patients. METHODS: This observational case-control study of Asian BC patients treated with chemotherapy included 161 FNc patients, 219 neutropenia patients, and 936 patients who did not develop neutropenia. A continuous PRS was calculated by summing weighted risk alleles associated with overall, estrogen receptor- (ER-) positive, and ER-negative BC risk. PRS distributions neutropenia or FNc cases were compared to controls who did not develop neutropenia using two-sample t-tests. Odds ratios (OR) and corresponding 95% confidence intervals were estimated for the associations between PRS (quartiles and per standard deviation (SD) increase) and neutropenia-related outcomes compared to controls. RESULTS: PRS distributions were not significantly different in any of the comparisons. Higher PRSoverall quartiles were negatively correlated with neutropenia or FNc. However, the associations were not statistically significant (PRS per SD increase OR neutropenia: 0.91 [0.79-1.06]; FNc: 0.87 [0.73-1.03]). No dose-dependent trend was observed for the ER-positive weighted PRS (PRSER-pos) and ER-negative weighted PRS (PRSER-neg). CONCLUSION: BC PRS was not strongly associated with chemotherapy-induced neutropenia or FNc.

Can Contrast-Enhanced Spectral Mammography (CESM) Reduce Benign Breast Biopsy?

Objectives: To evaluate the potential of contrast-enhanced spectral mammography (CESM) in reducing benign breast biopsy rate, thereby improving resource utilization. To explore its potential as a value-adding modality in the management of BI-RADS 4/5 lesions. Materials and Methods: This was a prospective study conducted between July 2016 and September 2018. Patients with BI-RADS 4/5 lesions detected on conventional imaging (mammogram, digital breast tomosynthesis, and ultrasound) were enrolled for adjunct CESM. Histopathologic correlation was done for all lesions. Additional suspicious lesions detected on CESM were all identified on second-look ultrasound and subsequently biopsied. Images were evaluated independently by two radiologists trained in breast imaging using BI-RADS classification. Presence of enhancement on CESM, BI-RADS score, and histopathology of each lesion were analyzed and tested with the chi-square/fisher-exact test for statistical significance. Results: The study included 105 lesions in 63 participants-1 man and 62 women, an average age of 53.7 ± 10.8 years. On CESM, 22 (20.9%) of the lesions did not show enhancement. All 22 lesions had been classified as BI-RADS 4A and were subsequently proven to be benign. Of the remaining 83 enhancing lesions, 54 (65.1%) were malignant and 29 (34.9%) were benign (p < 0.05). CESM detected 6 additional lesions which were not identified on initial conventional imaging. Four of these were proven malignant and were in a different quadrant than the primary lesion investigated. Conclusion: There is evidence that the absence of enhancement in CESM strongly favors benignity. It may provide the reporting radiologist with greater confidence in imaging assessment, especially in BI-RADS 4A cases, where a proportion of them are in actuality BI-RADS 3. Greater accuracy of BI-RADS grading can reduce nearly half of benign biopsies and allow better resource allocation. CESM also increases the detection rate of potentially malignant lesions, thereby changing the treatment strategies.

The therapeutic dilemma of idiopathic granulomatous mastitis.

INTRODUCTION: Idiopathic granulomatous mastitis (IGM) is a rare, benign, chronic breast condition that can cause repeated abscesses or mass formation in bilateral breasts. The condition can severely impact the quality of life of affected women. This study aims to evaluate effective treatment modalities, as well as understand the demographics and clinical presentation of patients with IGM. METHODS: An 11-year retrospective review was performed of patients diagnosed with IGM from 1 January 2008 to 31 December 2018 at a tertiary breast unit. RESULTS: A total of 77 patients were included in the study. The median age at presentation was 36 years old. IGM presented most commonly as a breast lump (98.1%). The median number of flares was 2 (1-12). Of the 77 patients, 68.8% (53) were treated with antibiotics, 50.6% (39) with steroids, and 44.2% (34) underwent surgery, in the course of their IGM treatment. Forty-five (59.2%) of the 76 patients with IGM required a multimodal treatment approach to achieve remission. There was no significant difference in the number of flares no matter the initial treatment (P=0.411), or subsequent treatment modality (P=0.343). Smokers had 10 times greater odds of having a "high flare" of IGM compared to those who did not smoke (P=0.031, odds ratio 10.444, 95% confidence interval 1.092-99.859). CONCLUSION: IGM is a clinical diagnosis. It is a rare, relapsing breast inflammatory condition that affects young females with no superior treatment modality. Smoking is associated with higher number of flares of IGM and should be discouraged in IGM patients.

Cohort profile: The Singapore Breast Cancer Cohort (SGBCC), a multi-center breast cancer cohort for evaluation of phenotypic risk factors and genetic markers.

This article aims to provide a detailed description of the Singapore Breast Cancer Cohort (SGBCC), an ongoing multi-ethnic cohort established with the overarching goal to identify genetic markers for breast cancer risk, prognosis and treatment response, as well as to understand the ethnic differences in disease risk and outcome in an Asian setting. The cohort comprises of breast cancer patients aged 21 years and above from six public hospitals which diagnose and treat nearly 76% breast cancer cases in Singapore. Self-reported data on sociodemographic and lifestyle, reproductive risk factors, medical history and family history of breast or ovarian cancer is collected using a structured questionnaire. Clinical data on tumour characteristics, and treatment modalities are obtained through medical record. Bio-specimens (blood or saliva) is collected at recruitment. Follow-up on survival information is done through routine linkage with the Registry of Births and Deaths. As of 31 December 2016, 7,768 subjects have been recruited to the study with 76% subjects contributed bio-specimens. The SGBCC provides a valuable platform which offers a unique, large and rich resource for new research ideas on breast cancer related phenotypic risk factors and genetic markers.

European polygenic risk score for prediction of breast cancer shows similar performance in Asian women.

Polygenic risk scores (PRS) have been shown to predict breast cancer risk in European women, but their utility in Asian women is unclear. Here we evaluate the best performing PRSs for European-ancestry women using data from 17,262 breast cancer cases and 17,695 controls of Asian ancestry from 13 case-control studies, and 10,255 Chinese women from a prospective cohort (413 incident breast cancers). Compared to women in the middle quintile of the risk distribution, women in the highest 1% of PRS distribution have a ~2.7-fold risk and women in the lowest 1% of PRS distribution has ~0.4-fold risk of developing breast cancer. There is no evidence of heterogeneity in PRS performance in Chinese, Malay and Indian women. A PRS developed for European-ancestry women is also predictive of breast cancer risk in Asian women and can help in developing risk-stratified screening programmes in Asia.

Majority of flat epithelial atypia diagnosed on biopsy do not require surgical excision.

BACKGROUND: Borderline risk lesions such as flat epithelial atypia (FEA) are increasingly being diagnosed on biopsy. The need for surgery is being debated. In this study, we determined the frequency of histological upgrade following a diagnosis of FEA on biopsy and evaluated potential predictive factors. METHODS: Retrospective review was done of 194 women who underwent biopsy of indeterminate lesions (total 195 lesions) that were diagnosed as FEA. The review covered a 10-year period. Cases where malignancy was also present together with FEA within the same biopsy cores were excluded. RESULTS: Lesions diagnosed as FEA on biopsy were mostly asymptomatic and presented as microcalcifications on mammogram. Flat epithelial atypia was the only abnormality detected in one-third of cases, was associated with a benign or another borderline lesion in another third and was associated with atypical ductal hyperplasia (ADH) in another third. Six patients (3.1%) were later found to have ductal carcinoma-in-situ (DCIS) at surgery. The presence of ADH in the biopsy was the only predictor of histological upgrade to malignancy (P = 0.04, OR 11.24, 95% CI 1.10 - 115.10), and was present in 5 of the 6 patients. Surgery was advised in the last patient because of radiology-pathology discordance. Thirty-six lesions (18.5%) were not excised and no interval progression or malignancy was found on follow up. CONCLUSION: Histological upgrade to malignancy was uncommon in lesions found on biopsy to be FEA. Non-operative management of biopsy-proven FEA can be considered in the absence of ADH and radiology-pathology discordance.

Adopting ambulatory breast cancer surgery as the standard of care in an asian population.

Introduction. Ambulatory surgery is not commonly practiced in Asia. A 23-hour ambulatory (AS23) service was implemented at our institute in March 2004 to allow more surgeries to be performed as ambulatory procedures. In this study, we reviewed the impact of the AS23 service on breast cancer surgeries and reviewed surgical outcomes, including postoperative complications, length of stay, and 30-day readmission. Methods. Retrospective review was performed of 1742 patients who underwent definitive breast cancer surgery from 1 March 2004 to 31 December 2010. Results. By 2010, more than 70% of surgeries were being performed as ambulatory procedures. Younger women (P < 0.01), those undergoing wide local excision (P < 0.01) and those with ductal carcinoma-in situ or early stage breast cancer (P < 0.01), were more likely to undergo ambulatory surgery. Six percent of patients initially scheduled for ambulatory surgery were eventually managed as inpatients; a third of these were because of perioperative complications. Wound complications, 30-day readmission and reoperation rates were not more frequent with ambulatory surgery. Conclusion. Ambulatory breast cancer surgery is now the standard of care at our institute. An integrated workflow facilitating proper patient selection and structured postoperativee outpatient care have ensured minimal complications and high patient acceptance.