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.

The Impact of Statin Use and Breast Cancer Recurrence - A Retrospective Study in Singapore.

Introduction: Statins, HMG-CoA reductase inhibitors, are commonly used cholesterol-lowering medications which are also increasingly recognized to have anti-cancer properties for various cancers, including breast cancer. Most clinical evidence supports a protective effect of statin on reducing breast cancer recurrence, particularly in hormone-receptor positive breast cancers.This study seeks to study the impact of statin use on breast cancer recurrence in an Asian population. Methods: This is a retrospective study of patients diagnosed with breast cancer at the National Cancer Centre and Singapore General Hospital from 2005-2015. Statin use was defined as use after surgery. Associations between statin use, breast cancer recurrence and overall survival were estimated using Cox proportional hazards regression with adjustment for age, TNM stage, grade, ER/HER2 status, and co-morbidities. Associations between statin-use and disease-specific survival were estimated using competing risks regression. Results: A total of 7858 females with breast cancer were studied, 1353(17.2%) were statin users, 6505(82.8%) were non-statin users, with a median follow-up of 8.67 years. Distribution of cancer stage, histology, molecular subtypes and grades were similar in both groups. Estrogen receptor(ER) positive (HR 0.57,95%CI 0.43-0.76,p<0.001) and HER2 negative (HR 0.74,95%CI 0.57-0.96,p=0.026) invasive cancers had a lower risk of recurrence in statin users. Statin users trended towards a long term recurrence-risk reduction (all subtypes,HR 0.48,p=0.002; ER-, HR 0.34,p=0.036; HER2+,HR 0.10,p=0.002). The risk-reduction benefit is not appreciated in statin users with DCIS, possibly due to small recurrence event numbers. Disease-specific survival benefit was seen in statin users with ER+ cancers (adjusted SHR 0.71,95%CI 0.53-0.96,p=0.027), especially ER+ invasive cancers (adjusted SHR 0.72, 95%CI 0.53-0.97,p=0.028), but with no statistically significant benefit in overall survival for statin users (all subtypes). Conclusion: This is the first known retrospective study on the effect of statin use and breast cancer recurrence in an Asian population. Similar to previous international studies, statin use is associated with a risk reduction in breast cancer recurrence. This is especially beneficial in patients who have ER+ and HER2- invasive breast cancer. Statin use is also associated with a reduced risk of breast cancer recurrence in all subtypes of breast cancer in the long term (>6 years post diagnosis).

Male breast cancer: a Singapore perspective.

INTRODUCTION: Male breast cancer (MBC) is rare, representing <1% of all breast cancers. Treatment recommendations have been extrapolated from trial data of female breast cancer patients. This study aims to report our institutional experience of MBC across a 20 year period, analyse the survival outcome and prognosis of this group against female breast cancer patients treated at the same centre. METHODS: Clinical, histopathological, treatment and survival data of male and female breast cancer patients treated between Jan 1999 and July 2019 at Singapore General Hospital and National Cancer Centre Singapore were identified and analysed. RESULTS: Fifty-seven male patients were identified. The median age at diagnosis was 63 years. Majority had invasive ductal carcinoma (86%) and presented at an early disease stage: 70.2% presented as Tis/T1/T2 and 49.1% had no axillary nodal involvement. 84.2% had a simple mastectomy with either a sentinel lymph node biopsy or axillary clearance. The median follow up was 5.69 years for males and 5.83 years for females. The median survival was 11.86 years for males and 16.3 years for females. At 5 years, overall survival (OS) was 69.9% (52.3-82.1%) and disease free survival (DFS) was 62.9% (44.9-76.5%) for males compared with OS 83.8% (83.21-84.39%) and DFS 74.5% (73.91-75.09%) for females. CONCLUSION: MBC remains understudied. Our institutional data indicates that good long term survival in South-East Asian patients can be achieved with treatment protocols that are similar to female breast cancer. More prospective studies are required.

Outcomes of Stage I and II Breast Cancer with Nodal Micrometastases Treated with Mastectomy without Axillary Therapy.

PURPOSE: Studies that report equivalent oncologic outcomes of sentinel lymph node biopsy (SLNB) alone versus axillary lymph node dissection (ALND) for T1-2N1mi breast cancers are heavily weighted with patients who received breast-conserving surgery (BCS). The impact of omitting ALND in N1mi patients treated with mastectomy is not well studied. It is also unknown if these patients would benefit from post-mastectomy radiotherapy (PMRT). This study reports the outcomes of patients with T1-2N1mi breast cancer treated by mastectomy without axillary therapy. METHODS: Patients who had T1-2N1mi breast cancer and underwent mastectomy from January 1998 to December 2018 were identified from our multi-institutional prospective database. Axillary recurrence rate (ARR), disease-free survival (DFS), and overall survival (OS) are reported. RESULTS: 260 patients with pT1-2N1mi breast cancer who had mastectomy were identified. They had either SLNB (35.4%) or ALND (64.6%). Majority of these patients received adjuvant systemic therapy (93.8%). 77 (29.6%) patients received radiotherapy, 31 after SLNB and 46 after ALND. At median follow-up of 61 months, ARR was 1.1% (n = 1) in the SLNB only group, vs. 0.6% (n = 1) in the ALND group (p = 0.752). DFS and OS were not significantly different between patients with SLNB alone versus ALND (p = 0.40 and p = 0.27, respectively). Among 92 patients who had SLNB only, no DFS or OS difference was observed with the use of PMRT. CONCLUSION: In T1-2N1mi patients with mastectomy and SLNB, axillary recurrences were rare. No statistically significant differences were noted between patients with SLNB, ALND, or PMRT. Our findings suggest that these patients may be safely treated without axillary therapy.

Fulminant gas-forming breast abscess associated with synergistic Veillonella infection.

We present a rare case of a rapidly fulminant and destructive breast abscess with gas production by the synergistic infection of Veillonella and Streptococcus species. To our knowledge, this is the first reported case of Veillonella infection in the breast. Early recognition, empiric antibiotic cover, aggressive surgical debridement, and drainage are necessary to avoid systemic septicemia. Staged reconstructive breast surgery allows for correction any resultant breast deformity.

Isolated invasive ductal carcinoma of the nipple-areolar complex: A rare occurrence yet to be reported in current literature.

Invasive ductal carcinoma of the nipple-areolar complex is exceedingly rare. Patients who present with bloody nipple discharge with or without the presence of Paget's disease constitute one-third of all symptomatic in situ patients. Only rarely does an invasive cancer cause nipple discharge in the absence of a clinical mass. Even more obscure is the case of the invasive cancer involving solely the nipple-areolar complex. Sir James Paget first described 'an eczematous change in the skin of the nipple preceding an underlying mammary cancer' in 1874, which is now known as Paget's disease, considered to be ductal carcinoma in situ of the nipple-areolar region. There are two competing theories as to the pathogenesis of Paget's disease of the breast-one suggests that Pagetoid cells are keratinocytes that have undergone malignant transformation. According to this theory, Paget's disease of the breast represents an in situ carcinoma of the skin-and that overlying skin changes and underlying malignancy are discontinuous. The second theory suggests that cells migrate along basement membranes and enter the epidermis and dermis of the nipple-areola complex. Pagetoid cells and underlying carcinomas demonstrate similar immunohistochemical staining patterns.

Evaluation of Long-Term Outcomes of Microsatellite Instability Status in an Asian Cohort of Sporadic Colorectal Cancers.

PURPOSE: Microsatellite instability in colorectal cancer (CRC) and its long-term outcomes remains poorly studied in Asians. We investigate the prognostic significance of microsatellite instability in an Asian population and assess its clinical impact in patients who undergo adjuvant chemotherapy. METHODS: Six hundred fifty-four consecutive CRC patients who underwent surgical resection between January 2010 and December 2012 were recruited. Survival was estimated using the Kaplan-Meier approach. Univariate Cox proportional hazard models were used to estimate the hazard ratios for variables associated with survival. A subgroup analyses was performed for stage III patients who underwent chemotherapy to evaluate the prognostic significance of microsatellite instability in this group. RESULTS: Five hundred ninety-one (90.4%) patients were microsatellite stable (MSS) while 63 (9.6%) were microsatellite instable (MSI). Three years recurrence-free survival (RFS) and disease-specific survival (DSS) were 83.7 versus 73.7% (p = 0.295) and 87.1 versus 91.2% (p = 0.307) in MSS and MSI tumors, respectively. Among stage III patients who received adjuvant therapy, MSI status was found to be an adverse prognostic factor for RFS (HR 2.74 (95% CI 1.43-5.26), p = 0.002). This remained significant on multivariate analysis (HR 2.38 (95% CI 1.15-4.93), p = 0.018). Adjuvant chemotherapy was associated with survival benefit for patients with MSS tumors (HR 0.35, 95% CI 0.17-0.69, p = 0.002) but not MSI tumors (HR 0.67, 95% CI 0.08-8.15, p = 0.750). CONCLUSIONS: MSI status is not a prognostic indicator in the general CRC population but appears to be an adverse prognostic indicator for RFS in stage III CRC patients who received adjuvant chemotherapy.