Clustering of HR + /HER2- breast cancer in an Asian cohort is driven by immune phenotypes.

Breast cancer exhibits significant heterogeneity, manifesting in various subtypes that are critical in guiding treatment decisions. This study aimed to investigate the existence of distinct subtypes of breast cancer within the Asian population, by analysing the transcriptomic profiles of 934 breast cancer patients from a Malaysian cohort. Our findings reveal that the HR + /HER2- breast cancer samples display a distinct clustering pattern based on immune phenotypes, rather than conforming to the conventional luminal A-luminal B paradigm previously reported in breast cancers from women of European descent. This suggests that the activation of the immune system may play a more important role in Asian HR + /HER2- breast cancer than has been previously recognized. Analysis of somatic mutations by whole exome sequencing showed that counter-intuitively, the cluster of HR + /HER2- samples exhibiting higher immune scores was associated with lower tumour mutational burden, lower homologous recombination deficiency scores, and fewer copy number aberrations, implicating the involvement of non-canonical tumour immune pathways. Further investigations are warranted to determine the underlying mechanisms of these pathways, with the potential to develop innovative immunotherapeutic approaches tailored to this specific patient population.

Age-specific breast and ovarian cancer risks associated with germline BRCA1 or BRCA2 pathogenic variants - an Asian study of 572 families.

Background: Clinical management of Asian BRCA1 and BRCA2 pathogenic variants (PV) carriers remains challenging due to imprecise age-specific breast (BC) and ovarian cancer (OC) risks estimates. We aimed to refine these estimates using six multi-ethnic studies in Asia. Methods: Data were collected on 271 BRCA1 and 301 BRCA2 families from Malaysia and Singapore, ascertained through population/hospital-based case-series (88%) and genetic clinics (12%). Age-specific cancer risks were estimated using a modified segregation analysis method, adjusted for ascertainment. Findings: BC and OC relative risks (RRs) varied across age groups for both BRCA1 and BRCA2. The age-specific RR estimates were similar across ethnicities and country of residence. For BRCA1 carriers of Malay, Indian and Chinese ancestry born between 1950 and 1959 in Malaysia, the cumulative risk (95% CI) of BC by age 80 was 40% (36%-44%), 49% (44%-53%) and 55% (51%-60%), respectively. The corresponding estimates for BRCA2 were 29% (26-32%), 36% (33%-40%) and 42% (38%-45%). The corresponding cumulative BC risks for Singapore residents from the same birth cohort, where the underlying population cancer incidences are higher compared to Malaysia, were higher, varying by ancestry group between 57 and 61% for BRCA1, and between 43 and 47% for BRCA2 carriers. The cumulative risk of OC by age 80 was 31% (27-36%) for BRCA1 and 12% (10%-15%) for BRCA2 carriers in Malaysia born between 1950 and 1959; and 42% (34-50%) for BRCA1 and 20% (14-27%) for BRCA2 carriers of the same birth cohort in Singapore. There was evidence of increased BC and OC risks for women from >1960 birth cohorts (p-value = 3.6 × 10-5 for BRCA1 and 0.018 for BRCA2). Interpretation: The absolute age-specific cancer risks of Asian carriers vary depending on the underlying population-specific cancer incidences, and hence should be customised to allow for more accurate cancer risk management. Funding: Wellcome Trust [grant no: v203477/Z/16/Z]; CRUK (PPRPGM-Nov20∖100002).

Exploring the health information-seeking practices of breast cancer patients in a middle-income country with a diverse ethnic population: a cross-sectional investigation.

Seeking health information is an important step for cancer patients to understand their condition and facilitate treatment. It also helps them deal with the unknown and aid in recovery. Therefore, it is vital to understand the factors that drive health information-seeking behavior. This study aims to achieve that objective in a localized context by surveying 421 breast cancer patients in an urban teaching hospital. The patients were presented with a 5-point questionnaire that explored their demography, health status, information-seeking behavior, and literacy level. The prevalence of health information-seeking initiatives reported was 60%. Patients with higher education (OR 3.31; 95% CI (1.39-7.87), p = 0.01), having their own business or were self-employed (OR 4.68; 95% CI (1.03-21.24), p = 0.046), and in a Medium 40 (M40) income level (OR 2.31; 95% CI (1.09-4.88), p = 0.03) and Top 20 (T20) level were more likely to seek health information. The mean e-Health Literacy Score (eHEALS) was 28.01 ± 5.0, with healthcare professionals having the highest level of trust (mean 4.22 ± 0.79) and most useful resource score (mean 4.21 ± 0.78). Even though Google was the most popular online search tool used by respondents, most of them seldom (23.77%) or had never (34.34%) discussed the online information they found with healthcare professionals. In conclusion, it is still best for patients to appraise the sought-after information with experts to avoid misinformation and treatment delay.

Factors associated with alteration of nipple or skin sensation and impact of duration of time following nipple-sparing mastectomy (NSM): an analysis of 460 cases with comparison of conventional versus endoscopic- or robotic-assisted NSM.

BACKGROUND: The current study aims to evaluate the nipple and skin sensation following nipple-sparing mastectomy (NSM) and identify patient-, surgical-, or treatment-related factors affecting nipple or skin sensation in this cohort. METHODS: Patients who received NSM with postoperative nipple and skin sensation test evaluation at a single institution over the past 10 years were retrospectively retrieved from a prospectively collected breast cancer surgery database. RESULTS: A total of 460 NSM procedures were included in this current study, with the mean age of 48.3 ± 9.1. Three-hundred eighty-three (83.3%) patients had breast reconstructions. One-hundred seventy-four (37.8%) received conventional NSM (C-NSM), 195 (42.4%) endoscopic-assisted NSM (E-NSM), and 91 (19.8%) robotic-assisted NSM (R-NSM) procedures. For nipple sensation assessment, 15 (3.3%) were grade 0, 83 (18.2%) grade I, 229 (49.7%) grade II, and 133 (28.9%) grade III (normal sensation), respectively, with mean grade score of 2.1 ± 0.7. The preserved (grade III) nipple sensation rate was 36.2% (63/174) in the C-NSM group, 26.7% (52/195) in the E-NSM group, and 19.7% (18/91) in the R-NSM group (P = 0.06). The "time since surgery to last evaluation" was significantly longer in the C-NSM group (45.6 ± 34 months) or E-NSM group (44.7 ± 35.8 months) as compared to R-NSM group (31.8 ± 16 months, P < 0.01). In multivariate analysis, peri-areolar incision showed higher grade of nipple sensation (OR: 2.1, P = 0.02) compared to upper outer quadrant incision, and longer follow-up time post-NSM showed significant improvement of nipple or skin sensation (> 60 months vs. ≦ 12 months: nipple odds ratio (OR) = 5.75, P < 0.01; skin, OR = 1.97, P < 0.05). CONCLUSION: Our current analysis showed some factors to be related to postoperative nipple or skin sensation, and longer "time after surgery" was associated with significant improvement of nipple and skin sensation in patients who received NSM, regardless of the surgical approaches. SYNOPSIS: Our current analysis showed a significant portion of patients with decrease or loss of nipple or skin sensation after nipple-sparing mastectomy (NSM). Several factors associated with preserved nipple or skin sensation were identified, including age, surgical methods, surgical wound location, and association of time from surgery showing that improvement of partial nipple or skin sensation was evident after a longer follow-up.

Breaking the Barrier: A Study on Multi-drug Resistance in Breast Abscess at an Academic Malaysian Hospital.

BACKGROUND: In recent years, the increase in antibiotics usage locally has led to a worrying emergence of multi-drug resistant organisms (MDRO), with the Malaysian prevalence rate of methicillin-resistant Staphylococcus aureus (MRSA) ranging from 17.2 to 28.1% between 1999 and 2017. A study has shown that 7% of all non-lactational breast abscesses are caused by MRSA. Although aspiration offers less morbidities compared to surgical drainage, about 20% of women infected by MRSA who initially underwent aspiration subsequently require surgical drainage. This study is conducted to determine the link between aetiology, antimicrobial resistance pattern and treatment modalities of breast abscesses. METHODS: Retrospective study of reviewing microbiology specimens of breast abscess patients treated at Universiti Malaya Medical Centre from 2015 to 2020. Data collected from microbiology database and electronic medical records were analysed using SPSS V21. RESULT: A total of 210 specimens from 153 patients were analysed. One-fifth (19.5%) of the specimens isolated were MDRO. Lactational associated infections had the largest proportion of MDR in comparison to non-lactational and secondary infections (38.5%, 21.7%, 25.7%, respectively; p = 0.23). Staphylococcus epidermidis recorded the highest number of MDR (n = 12) followed by S. aureus (n = 8). Adjusted by aetiological groups, the presence of MDRO is linked to failure of single aspirations (p = 0.554) and significantly doubled the risk of undergoing surgical drainage for resolution (p = 0.041). CONCLUSION: MDR in breast abscess should be recognised as an increasing healthcare burden due to a paradigm shift of MDRO and a rise of resistance cases among lactational associated infection that were vulnerable to undergo surgical incision and drainage for resolution.

Classification and assessment techniques of breast ptosis: A systematic review.

BACKGROUND: Breast ptosis is characterized by the inferolateral descent of the glandular area and nipple-areola complex. A high degree of ptosis may negatively impact a woman's attractiveness and self-confidence. There are various classifications and measurement techniques for breast ptosis used as references in the medical and garment industry. A practical and comprehensive classification will provide accurate standardized definitions of the degrees of ptosis to facilitate the development of corrective surgeries and well-fitting undergarments for women in need. METHODS: A systematic review on the classification and assessment techniques to measure breast ptosis was carried out based on the Preferred Reporting Items for Systemic Reviews and Meta-Analyses (PRISMA) guidelines. The risk of bias was assessed using the modified Newcastle-Ottawa scale for observational studies, whereas the Revised Cochrane risk-of-bias tool for randomized trials (RoB2) was used to evaluate randomized studies. RESULTS: Of 2550 articles identified in the literature search, 16 observational and 2 randomized studies describing the classification and assessment techniques of breast ptosis were included in the review. A total of 2033 subjects were involved. Half of the total observational studies had a Newcastle-Ottawa scale score of 5 and above. In addition, all randomized trials recorded a low overall bias. CONCLUSION: A total of 7 classifications and 4 measurement techniques for breast ptosis were identified. However, most studies did not demonstrate a clear derivation of sample size beside lacking robust statistical analysis. Hence, further studies that apply the latest technology to combine the strength of previous assessment techniques are needed to develop better classification system that is applicable to all affected women.

Association between pre-existing cardiometabolic comorbidities and the pathological profiles of breast cancer at initial diagnosis: a cross sectional study.

The presence of comorbidities has been associated with later stages of breast cancer diagnosis. It is unclear whether biological mechanisms are partly responsible. We examined the association between the presence of pre-existing comorbidities and tumour profile at initial diagnosis with breast cancer. Data for the present analysis were derived from a prior inception cohort study comprising 2,501 multiethnic women, newly diagnosed with breast cancer between 2015 and 2017 in four hospitals across Klang Valley. At the inception of the cohort, medical and drug histories, height, weight and blood pressure were recorded. Blood samples were taken to measure serum lipid and glucose. Modified Charlson Comorbidity Index (CCI) was calculated using data extracted from medical records. The association of CCI as well as specific comorbidities, with pathological breast cancer profile was analysed. Higher comorbidity burden, namely cardiometabolic conditions were associated with unfavourable pathological features including larger tumours, involvement of >9 axillary lymph nodes, distant metastasis and human epidermal growth factor receptor 2 overexpression. These associations remained largely significant following multivariable analyses. Specifically, diabetes mellitus was independently associated with high nodal metastasis burden. Low level of high-density lipoprotein was associated with larger tumours (>5 cm), and distant metastasis. Evidence from this study seems to support the hypothesis that the later stages of breast cancer diagnosis in women with (cardiometabolic) comorbidities may be partially explained by underlying pathophysiological events.

"An Unusual Pattern of Metastasis" Metastatic Malignant Thymoma Presented with Breast Lump: A Case Report and Literature Review.

Metastatic lesions to the breast from extramammary malignant neoplasms are rare and reported account for 0.5-6.6% of all breast malignancies. Distant metastasis of thymoma is even rarer, especially to extrathoracic regions. We reported a woman with invasive malignant thymoma postneoadjuvant and resection of the thymoma, who developed breast metastasis 7 years later. Breast imaging showed high-density lesion with no intralesional microcalcifications and no significant axillary lymphadenopathy. Core biopsy and histopathology proved the lesion to be metastatic thymic carcinoma. Despite rarity, breast lumps with underlying extramammary malignancy should raise the suspicious of breast metastasis.

Discriminatory Ability and Clinical Utility of the AJCC7 and AJCC8 Staging Systems for Breast Cancer in a Middle-Income Setting.

(1) Background: Differences in access to biomarker testing and cancer treatment in resource-limited settings may affect the clinical utility of the AJCC8 staging system compared to the anatomical AJCC7 system. (2) Methods: A total of 4151 Malaysian women who were newly diagnosed with breast cancer from 2010 to 2020 were followed-up until December 2021. All patients were staged using the AJCC7 and AJCC8 systems. Overall survival (OS) and relative survival (RS) were determined. Concordance-index was used to compare the discriminatory ability between the two systems. (3) Results: Migration from the AJCC7 to AJCC8 staging system resulted in the downstaging of 1494 (36.0%) patients and the upstaging of 289 (7.0%) patients. Approximately 5% of patients could not be staged using the AJCC8 classification. Five-year OS varied between 97% (Stage IA) and 66% (Stage IIIC) for AJCC7, and 96% (Stage IA) and 60% (Stage IIIC) for AJCC8. Concordance-indexes for predicting OS using the AJCC7 and AJCC8 models were 0.720 (0.694-0.747) and 0.745 (0.716-0.774), and for predicting RS they were 0.692 (0.658-0.728) and 0.710 (0.674-0.748), respectively. (4) Conclusions: Given the comparable discriminatory ability between the two staging systems in predicting the stage-specific survival of women with breast cancer in the current study, the continued use of the AJCC7 staging system in resource-limited settings seems pragmatic and justifiable.

Comparison of Clinical Outcomes Between Low- and High-Risk Groups of Early Breast Cancer Patients Treated with Intraoperative Radiotherapy in Addition to External Beam Radiation: A Multi-Centre Prospective Study.

BACKGROUND: There is a paucity of data on the use of intraoperative radiotherapy (IORT) with low-energy X-rays in Malaysian women with early breast cancer. The aim of this study is to evaluate the clinical, cosmetic, and patient-reported outcomes in low- and high-risk early breast cancer patients treated with breast conserving surgery (BCS) and IORT. METHODOLOGY: Patients suitable for BCS who were treated with IORT between January 2016 and June 2019 from three centres were analysed. They were divided into low-risk and high-risk groups based on the risk of recurrence according to the TARGeted Intraoperative radioTherapy (TARGIT) A and B study criteria. Outcomes of interest included local recurrence, wound complications, and radiation toxicity, with a subset analysed for cosmetic and patient-reported outcomes. RESULTS: Within a median follow-up of 31 months, there were 104 and 211 patients in the low- and high-risk groups, respectively. No significant difference was observed in local recurrence rates (low-risk, 1.0% vs. high-risk, 1.4%; p = 1.000). Both cohorts exhibited low frequencies of severe wound complications ranging between 1.4 and 1.9%. No major radiation toxicities were reported in either group. In the subgroup analysis, low-risk patients had significantly better mean scores in the subscales of inframammary fold and scar. Based on the BREAST-Q patient-reported outcomes questionnaire, seven out of nine parameters were scored similarly between both groups with no significant difference. CONCLUSION: This study showed that the use of IORT in both low- and high-risk early breast cancers is efficacious and safe with low recurrence rates and an acceptable toxicity profile.

Mindful gratitude journaling: psychological distress, quality of life and suffering in advanced cancer: a randomised controlled trial.

CONTEXT: Numerous studies have shown that gratitude can reduce stress and improve quality of life. OBJECTIVE: Our study aimed to examine the effect of mindful gratitude journaling on suffering, psychological distress and quality of life of patients with advanced cancer. METHODS: We conducted a parallel-group, blinded, randomised controlled trial at the University of Malaya Medical Centre, Malaysia. Ninety-two adult patients with advanced cancer, and an overall suffering score ≥4/10 based on the Suffering Pictogram were recruited and randomly assigned to either a mindful gratitude journaling group (N=49) or a routine journaling group (N=43). RESULTS: After 1 week, there were significant reductions in the overall suffering score from the baseline in both the intervention group (mean difference in overall suffering score=-2.0, 95% CI=-2.7 to -1.4, t=-6.125, p=0.000) and the control group (mean difference in overall suffering score=-1.6, 95% CI=-2.3 to -0.8, t=-4.106, p=0.037). There were also significant improvements in the total Hospital Anxiety and Depression Scale score (mean difference=-3.4, 95% CI=-5.3 to -1.5, t=-3.525, p=0.000) and the total Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being score (mean difference=7.3, 95% CI=1.5 to 13.1, t=2.460, p=0.014) in the intervention group after 7 days, but not in the control group. CONCLUSION: The results provide evidence that 7 days of mindful gratitude journaling could positively affect the state of suffering, psychological distress and quality of life of patients with advanced cancer. TRIAL REGISTRATION NUMBER: The trial was registered with the Australian and New Zealand Clinical Trials Registry (ACTRN1261800172191) and conducted in accordance with the Declaration of Helsinki.

A rare case of persistent large cystic breast tumor mimicking as malignant cystic breast cancer.

Breast cyst, especially galactocele is usually benign. Needle aspiration or surgical removal are both diagnostic and therapeutic. Mastectomy is not necessary even if the whole breast is affected, but surgeons need to be vigilant. We describe a rare case of persistent and large breast cyst.

Impact of preoperative magnetic resonance imaging on surgery and eligibility for intraoperative radiotherapy in early breast cancer.

We looked at the usefulness of magnetic resonance imaging (MRI) in decision-making and surgical management of patients selected for intraoperative radiotherapy (IORT). We also compared lesion size measurements in different modalities (ultrasound (US), mammogram (MMG), MRI) against pathological size as the gold standard. 63 patients eligible for IORT based on clinical and imaging criteria over a 34-month period were enrolled. All had MMG and US, while 42 had additional preoperative MRI for locoregional preoperative staging. Imaging findings and pathological size concordances were analysed across the three modalities. MRI changed the surgical management of 5 patients (11.9%) whereby breast-conserving surgery (BCS) and IORT was cancelled due to detection of satellite lesion, tumor size exceeding 30mm and detection of axillary nodal metastases. Ten of 42 patients (23.8%) who underwent preoperative MRI were subjected to additional external beam radiotherapy (EBRT); 7 due to lymphovascular invasion (LVI), 2 due to involved margins, and 1 due to axillary lymph node metastatic carcinoma detected in the surgical specimen. Five of 21 (23.8%) patients without prior MRI were subjected to additional EBRT post-surgery; 3 had LVI and 2 had involved margins. The rest underwent BCS and IORT as planned. MRI and MMG show better imaging-pathological size correlation. Significant increase in the mean 'waiting time' were seen in the MRI group (34.1 days) compared to the conventional imaging group (24.4 days). MRI is a useful adjunct to conventional imaging and impacts decision making in IORT. It is also the best imaging modality to determine the actual tumour size.

Adverse events following immunization and psychological distress among cancer patients/survivors following vaccination against SARS-CoV-2 infection.

Purpose: This study aims to describe the adverse events following immunization (AEFIs) of SARS-CoV-2 vaccination in cancer patients/survivors associated with their psychological distress. Methods: A cross-sectional study was conducted to assess AEFIs after the receipt of SARS-CoV-2 vaccines in cancer patients/survivors attending a university hospital in Malaysia. Psychological distress was measured using the Hospital Anxiety and Depression Scale (HADS) before and after the first and second doses of COVID-19 vaccine. Results: A total of 217 complete responses were received. Compared with before vaccination, both HADS Anxiety (HADS-A) and HADS Depression (HADS-D) scores were significantly reduced after the first and second dose of the SARS-CoV-2 vaccine. Most of the participants had mild-or-moderate systemic and local AEFIs, with the most common being pain at the injection site, tiredness, and headache for both the first and second doses of the vaccine. Positive correlations between the total AEFI score and HADS-A (r = 0.309, p < 0.001) and HADS-D (r = 0.214, p = 0.001) scores were observed after the first dose of the SARS-CoV-2 vaccine. Similarly, positive associations were observed between the total AEFI score and HADS-A (r = 0.305, p < 0.001) and HADS-D (r = 0.235, p < 0.001) scores after the second dose of the SARS-CoV-2 vaccine. Conclusion: Mild-to-moderate AEFIs found in this study help address vaccine hesitancy in cancer patients/survivors. Receiving the SARS-CoV-2 vaccine had a positive effect on decreasing psychological distress in cancer patients/survivors. High severity of an AEFI was associated with higher anxiety and depressive symptoms.

Psychological distress among elderly surgical patients who had their surgery postponed during the COVID-19 pandemic.

BACKGROUND: Many institutions withheld elective lists and triaged surgeries during the peak of coronavirus disease 2019 (COVID-19) pandemic. As a result, older surgical patients have had to wait for rescheduled dates in a long waitlist. This study aimed to identify the psychological impact in these patients when they returned for surgery. METHODS: This was a cross-sectional study which included 153 patients aged ≥ 65 years undergoing elective surgery. Trained interviewers recruited and assessed psychological status pre-operatively with two validated questionnaires - Hospital Anxiety and Depression Scale (HADS) and 36-item Short Form Health Survey (SF-36). Specific questions were asked about their postponed surgeries, appetite and fear. RESULTS: A total of 36 out of 153 (23.5%) patients had their procedures deferred during the first wave of COVID-19 pandemic. Postponed cases were significantly based on the nature of surgery (p = 0.002), cancer diagnosis (p = 0.006) and surgical specialty (p = 0.023). Median HADS scores were higher for patients who were postponed (2.00 versus 4.00 for anxiety, p = 0.180 and 0.00 versus 1.00 for depression, p = 0.424) although no statistical significance was shown. In the whole study population, anxiety was a significant predictor for depression and vice versa (p < 0.001) with other predictive risk factors for anxiety that were age ≥ 85 years old (odds ratio [OR] 6.14, p = 0.018), female (OR 2.41, p = 0.024), cancer (OR 2.19, p = 0.039) and major surgery (OR 2.39, p = 0.023). Similarly, older patients ≥ 85 years old (OR 10.44, p = 0.003) and female (OR 6.07, p = 0.006) had higher risk for depression. Both anxiety and depression were significant risks for loss of appetite (p = 0.005 and 0.001). Lastly, the fear of disease progression due to rescheduling was more frequent in cancer patients (p = 0.035). CONCLUSION: The mental health and disease burden of older surgical patients should be taken into careful consideration when cases need to be postponed in our healthcare system.

Association Between Adherence to Clinical Practice Guidelines for Adjuvant Therapy for Breast Cancer and Survival in a Resource-Limited Setting.

PURPOSE: Addressing unwarranted clinical variation in oncology practices is expected to lead to improved cancer outcomes. Particularly, the application and impact of treatment guidelines on breast cancer outcomes are poorly studied in resource-limited settings. We measured adherence to a set of locally developed adjuvant treatment guidelines in a middle-income setting. Importantly, the impact of guidelines adherence on survival following breast cancer was determined. METHODS: Data of 3,100 Malaysian women with nonmetastatic breast cancer diagnosed between 2010 and 2017 were analyzed. Adherence to the Malaysian Clinical Practice Guidelines for Management of Breast Cancer second Edition was measured. Outcomes comprised overall survival and event-free survival. RESULTS: Guideline adherence for chemotherapy, radiotherapy, hormonal therapy, and targeted therapy were 61.7%, 79.2%, 85.1%, and 26.2%, respectively. Older age was generally associated with lower adherence to guidelines. Compared with patients who were treated according to treatment guidelines, overall survival and event-free survival were substantially lower in patients who were not treated accordingly; hazard ratios for all-cause mortality were 1.69 (95% CI, 1.29 to 2.22), 2.59 (95% CI, 1.76 to 3.81), 3.08 (95% CI, 1.94 to 4.88), and 4.48 (95% CI, 1.98 to 10.13) for chemotherapy, radiotherapy, hormone therapy, and targeted therapy, respectively. Study inferences remain unchanged following sensitivity analyses. CONCLUSION: Our study findings appear to suggest that adherence to treatment guidelines that have been adapted for resource-limited settings may still provide effective guidance in improving breast cancer outcomes.

Characterisation of protein-truncating and missense variants in PALB2 in 15 768 women from Malaysia and Singapore.

BACKGROUND: Rare protein-truncating variants (PTVs) in partner and localiser of BRCA2 (PALB2) confer increased risk to breast cancer, but relatively few studies have reported the prevalence in South-East Asian populations. Here, we describe the prevalence of rare variants in PALB2 in a population-based study of 7840 breast cancer cases and 7928 healthy Chinese, Malay and Indian women from Malaysia and Singapore, and describe the functional impact of germline missense variants identified in this population. METHODS: Mutation testing was performed on germline DNA (n=15 768) using targeted sequencing panels. The functional impact of missense variants was tested in mouse embryonic stem cell based functional assays. RESULTS: PTVs in PALB2 were found in 0.73% of breast cancer patients and 0.14% of healthy individuals (OR=5.44; 95% CI 2.85 to 10.39, p<0.0001). In contrast, rare missense variants in PALB2 were not associated with increased risk of breast cancer. Whereas PTVs were associated with later stage of presentation and higher-grade tumours, no significant association was observed with missense variants in PALB2. However, two novel rare missense variants (p.L1027R and p.G1043V) produced unstable proteins and resulted in a decrease in homologous recombination-mediated repair of DNA double-strand breaks. CONCLUSION: Despite genetic and lifestyle differences between Asian and other populations, the population prevalence of PALB2 PTVs and associated relative risk of breast cancer, are similar to those reported in European populations.

Baseline cardiovascular comorbidities, and the influence on cancer treatment decision-making in women with breast cancer.

PURPOSE: To measure the baseline prevalence of cardiovascular disease (CVD), its modifiable and non-modifiable risk factors in breast cancer patients, and determine their association with adjuvant treatment decision-making. METHOD: From 2016 to 2017, 2,127 women newly-diagnosed with breast cancer were prospectively recruited. Participants' cardiovascular biomarkers were measured prior to adjuvant treatment decision-making. Clinical data and medical histories were obtained from hospital records. Adjuvant treatment decisions were collated 6-8 months after recruitment. A priori risk of cardiotoxicity was predicted using the Cardiotoxicity Risk Score. RESULTS: Mean age was 54 years. Eighty-five patients had pre-existing cardiac diseases and 30 had prior stroke. Baseline prevalence of hypertension was 47.8%. Close to 20% had diabetes mellitus, or were obese. Dyslipidaemia was present in 65.3%. The proportion of women presenting with ≥2 modifiable CVD risk factors at initial cancer diagnosis was substantial, irrespective of age. Significant ethnic variations were observed. Multivariable analyses showed that pre-existing CVD was consistently associated with lower administration of adjuvant breast cancer therapies (odds ratio for chemotherapy: 0.32, 95% confidence interval: 0.17-0.58). However, presence of multiple risk factors of CVD did not appear to influence adjuvant treatment decision-making. In this study, 63.6% of patients were predicted to have high risks of developing cardiotoxicities attributed to a high baseline burden of CVD risk factors and anthracycline administration. CONCLUSION: While recent guidelines recommend routine assessment of cardiovascular comorbidities in cancer patients prior to initiation of anticancer therapies, this study highlights the prevailing gap in knowledge on how such data may be used to optimise cancer treatment decision-making.

Outcomes after mastectomy with immediate breast reconstruction for breast cancer in a multiethnic, middle-income Asian setting.

BACKGROUND: Although immediate breast reconstruction is increasingly becoming popular worldwide, evidence from resource-limited settings is scarce. We investigated factors associated with immediate breast reconstruction in a multiethnic, middle-income Asian setting. Short-term surgical complications, timing of initiation of chemotherapy, and survival outcomes were compared between women undergoing mastectomy alone and their counterparts receiving immediate breast reconstruction. METHODS: This historical cohort study included women who underwent mastectomy after diagnosis with stage 0 to stage IIIa breast cancer from 2011 to 2015 in a tertiary hospital. Multivariable regression analyses were used to assess factors associated with immediate breast reconstruction and to measure clinical outcomes. RESULT: Out of 790 patients with early breast cancer who had undergone mastectomy, only 68 (8.6%) received immediate breast reconstruction. Immediate breast reconstruction was independently associated with younger age at diagnosis, recent calendar years, Chinese ethnicity, higher education level, and invasive ductal carcinomas. Although immediate breast reconstruction was associated with a higher risk of short-term local surgical complications (adjusted odds ratio: 3.58 [95% confidence interval 1.75-7.30]), there were no significant differences in terms of delay in initiation of chemotherapy, 5-year disease-free survival, and 5-year overall survival between both groups in the multivariable analyses. CONCLUSION: Although associated with short-term surgical complications, immediate breast reconstruction after mastectomy does not appear to be associated with delays in initiation of chemotherapy, recurrence, or mortality after breast cancer. These findings are valuable in facilitating shared surgical decision-making, improving access to immediate breast reconstruction, and setting priorities for surgical trainings in middle-income settings.

Evaluation of skin dose and skin toxicity in patients undergoing intraoperative radiotherapy for early breast cancer.

PURPOSE: This study aims to evaluate in vivo skin dose delivered by intraoperative radiotherapy (IORT) and determine the factors associated with an increased risk of radiation-induced skin toxicity. METHODOLOGY: A total of 21 breast cancer patients who underwent breast-conserving surgery and IORT, either as IORT alone or IORT boost plus external beam radiotherapy (EBRT), were recruited in this prospective study. EBT3 film was calibrated in water and used to measure skin dose during IORT at concentric circles of 5 mm and 40 mm away from the applicator. For patients who also had EBRT, the maximum skin dose was estimated using the radiotherapy treatment planning system. Mid-term skin toxicities were evaluated at 3 and 6 months post-IORT. RESULTS: The average skin dose at 5 mm and 40 mm away from the applicator was 3.07 ± 0.82 Gy and 0.99 ± 0.28 Gy, respectively. Patients treated with IORT boost plus EBRT received an additional skin dose of 41.07 ± 1.57 Gy from the EBRT component. At 3 months post-IORT, 86% of patients showed no evidence of skin toxicity. However, the number of patients suffering from skin toxicity increased from 15% to 38% at 6 months post-IORT. We found no association between the IORT alone or with the IORT boost plus EBRT and skin toxicity. Older age was associated with increased risk of skin toxicities. A mathematical model was derived to predict skin dose. CONCLUSION: EBT3 film is a suitable dosimeter for in vivo skin dosimetry in IORT, providing patient-specific skin doses. Both IORT alone and IORT boost techniques resulted in similar skin toxicity rates.