A comprehensive analysis of imaging features and clinical characteristics to differentiate malignant from non-malignant mammographic architectural distortion.

Background: Mammographic architectural distortion (AD) is usually subtle and has variable presentations and causes, which poses a diagnostic challenge for breast radiologists and consequently a complex decision-making challenge for clinicians and patients. Presently, there is no reliable imaging standard to differentiate between malignant and benign ADs preoperatively. This study aimed to perform a comprehensive analysis of detailed mammographic and ultrasonographic features and clinical characteristics to enhance the diagnostic and differential efficacy for AD lesions. The findings have the potential to boost the diagnostic confidence of breast radiologists when encountering with AD lesions and could be instrumental in refining clinical management strategies for ADs. Methods: This retrospective study included consecutive female patients with ADs on screening or diagnostic mammography from January 6, 2015, to December 28, 2018. The patient's clinical data, mammographic and ultrasonographic or "second look" ultrasonographic findings, and pathological results were reviewed. The continuous variables were analyzed using the t-test. The categorical variables were assessed using the Chi-square test or two-tailed Fisher's exact test. Logistic regression analyses were conducted to evaluate potential risk factors for pathologically proven malignant ADs. Machine learning model based on multimodal clinical and imaging features was constructed using R software. Results: Ultimately, 344 patients with 346 AD lesions were enrolled in the study (mean age: 47.40±10.07 years; range, 19-84 years). Of the ADs, 228 were malignant and 118 were non-malignant. Palpable AD on mammography was more likely to indicate malignancy than non-palpable AD (83.43% vs. 49.15%, P<0.001). AD associated with other mammographic findings was more likely to be malignant than pure AD (73.58% vs. 59.36%, P=0.005). Ultrasonography (US) correlates were observed in 345 of these 346 AD lesions. Among these US correlates, 63 (18.26%, 63/345) were detected by "second look" ultrasound. For the US correlates, the mammographic ADs that appeared as non-mass-like hypoechoic areas and masses on US were more likely to be malignant than those that appeared as other abnormalities (P<0.001). The sensitivity, specificity and diagnostic accuracy of the eXtreme Gradient Boosting (XGBoost) model based on clinical and comprehensive imaging features in differentiation of AD lesions in the validation set were 66.46%, 94.23% and 78.9%, respectively, and the AUC was 0.886 (95% confidence interval: 0.825-0.947). Conclusions: The application of mammograms-guided "second-look" ultrasound could enhance the detection of US correlates, particularly non-mass-like features. The comprehensive analysis based on clinical and multimodal imaging features could be beneficial in improving the diagnostic and differential efficacy for AD lesions detected on mammography and instrumental in refining clinical management strategies for ADs.

Outcomes in Nonmetastatic Hormone Receptor-Positive HER2-Negative Pure Mucinous Breast Cancer: A Multicenter Cohort Study.

BACKGROUND: Although considered a favorable subtype, pure mucinous breast cancer (PMBC) can recur, and evidence for adjuvant therapy is limited. We aimed to compare outcomes of nonmetastatic PMBC with invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) to address these uncertainties. METHODS: Individual patient-level data from 6 centers on stage I-III hormone receptor-positive and HER2-negative PMBC, IDC, and ILC were used to analyze recurrence-free interval (RFI), recurrence-free survival (RFS), and overall survival (OS), and to identify prognostic factors for PMBC. RESULTS: Data from 20,684 IDC cases, 1,475 ILC cases, and 943 PMBC cases were used. Median follow-up was 6.6 years. Five-year RFI, RFS, and OS for PMBC were 96.1%, 94.9%, and 98.1%, respectively. On multivariable Cox regression, PMBC demonstrated superior RFI (hazard ratio [HR], 0.59; 95% CI, 0.43-0.80), RFS (HR, 0.70; 95% CI, 0.56-0.89), and OS (HR, 0.71; 95% CI, 0.53-0.96) compared with IDC. ILC showed comparable outcomes to IDC. Fewer than half (48.7%) of recurrences in PMBC were distant, which was a lower rate than for IDC (67.3%) and ILC (80.6%). In contrast to RFI, RFS events were driven more by non-breast cancer deaths in older patients. Significant prognostic factors for RFI among PMBC included positive lymph node(s) (HR, 2.42; 95% CI, 1.08-5.40), radiotherapy (HR, 0.44; 95% CI, 0.23-0.85), and endocrine therapy (HR, 0.25; 95% CI, 0.09-0.70). No differential chemotherapy associations with outcomes were detected across PMBC subgroups by nodal stage, tumor size, and age. A separate SEER database analysis also did not find any association of improved survival with adjuvant chemotherapy in these subgroups. CONCLUSIONS: Compared with IDC, PMBC demonstrated superior RFI, RFS, and OS. Lymph node negativity, adjuvant radiotherapy, and endocrine therapy were associated with superior RFI. Adjuvant chemotherapy was not associated with better outcomes.

A WeChat-based nursing intervention program improves the postoperative rehabilitation of breast cancer patients: results from a randomized controlled trial.

Background: In postoperative setting, breast cancer (BC) patients can experience adverse effects, including fatigue, sleep disorders, and pain, which substantially affect their health-related quality of life (HRQoL). This study sought to assess the effectiveness of a WeChat-based multimodal nursing program (WCBMNP) that was specifically designed for the rehabilitation of women following BC surgery. Methods: BC patients were randomly, single-blinded allocated to either the intervention (n=62) or control (n=63) cohorts. Over a period of 6 months (24 weeks), the intervention cohort received a WCBMNP in addition to routine nursing care, while the control cohort received routine nursing care only. To evaluate patients' fear of cancer recurrence (FCR), their overall fear score was assessed using the Japanese version of the Concerns About Recurrence Scale (CARS-J) for primary outcome. The initial outcome (HRQoL) and secondary results, such as fatigue, sleep, and pain, were examined using the Functional Assessment of Cancer Therapy-Breast (FACT-B, version 4.0) and Nursing Rating Scale (NRS), respectively. Results: Two hundred and ten participants, 85 participants were excluded. Compared to the controls (n=63), the intervention cohort (n=62) showed statistically significant improvements in their CARS-J scores. The intervention cohort aggregate scores on the FACT-B improved significantly but were affected by the compounding influences of cohort dynamics, temporal progression, and their interaction. Similar improvements were observed in the social/family and functional well-being domains. Emotional well-being was improved based on the effects of time and group-time interaction. In the intervention cohort, the "BC-specific subscale for additional concerns" was affected by group and time, whereas physical well-being was only affected by time. Conversely, there were no statistically significant changes in the variables of fatigue, sleep, and pain. Conclusions: The WCBMNP reduced FCR and significantly increased the HRQoL of female patients with BC postoperatively. The WCBMNP could be implemented as a postoperative rehabilitation intervention in this patient population to improve outcomes. Trial Registration: Chinese Clinical Trial Registry (ChiCTR2400081557).

Determining the Need for Metastatic Staging in Patients with Bilateral Breast Cancers.

Introduction: Bilateral breast cancers (BBC) diagnosed at an interval apart are uncommon. While metastatic staging guidelines are established in patients with unilateral breast cancer, its role in BBC diagnosed at an interval apart is unclear. We aim to identify the subgroup who would benefit from metastatic staging at contralateral cancer diagnosis. Methods: Eligible patients were divided into three categories: (A) ipsilateral invasive cancer and contralateral ductal carcinoma in situ (DCIS), (B) bilateral invasive cancers and (C) ipsilateral DCIS and contralateral invasive cancer and reviewed retrospectively. We excluded patients with bilateral DCIS, synchronous BBC diagnosed within 6 months from first cancer, patients who were stage IV at first cancer diagnosis and patients with recurrence prior to contralateral cancer. Results: Of 4516 newly diagnosed breast cancer patients, 79 patients were included. Systemic metastasis occurred in 15.6% of patients in Group B. Having nodal positivity of either cancer which were diagnosed ≤30 months apart and nodal positivity of only the contralateral cancer when diagnosed >30 months apart was significantly associated with systemic metastasis (p = 0.0322). Conclusions: Both the nodal status and a 30 months cut-off time interval between the two cancers can be used to identify patients who will benefit from metastatic staging. This finding requires validation in larger studies.

Use of axillary ultrasound to guide breast cancer management in the genomic assay era.

INTRODUCTION: Chemotherapy is conventionally offered to non-stage IV breast cancer patients with metastatic nodes. However, the RxPONDER trial showed that chemotherapy can be omitted in selected patients with 1-3 metastatic nodes if the 21-gene assay recurrence score is ≤25. We aimed to investigate if axillary ultrasound can identify this group of patients with limited nodal burden so that they can undergo upfront surgery followed by gene assay testing, to potentially avoid chemotherapy. METHODS: T1-3, node positive, hormone receptor-positive and HER2-negative breast cancer patients ≥50 years old with axillary lymph node dissection (ALND) were reviewed from 2 centres. Patients with neoadjuvant chemotherapy and bilateral cancers were excluded. Number of ultrasound-detected abnormal axillary nodes, demographic and histological parameters were correlated with the number of metastatic nodes found on ALND. RESULTS: 138 patients were included, 59 (42.8%) and 79 (57.2%) patients had 1-3 and >3 metastatic nodes on ALND respectively. On logistic regression and ROC analysis, the number of ultrasound-detected abnormal nodes was significant (p < 0.001) for predicting limited nodal burden (ROC AUC = 0.7135). Probabilities of <4 metastatic nodes with ultrasound cut-offs of 5, 6 and 8 abnormal nodes were 0.057, 0.026 and 0.005 respectively, with 100% specificity. CONCLUSION: A cut-off of ≤5 ultrasound-detected abnormal nodes can distinguish between patients with limited versus high nodal burden, with high specificity. Hence, incorporating the number of abnormal ultrasound-detected nodes into clinical practice may prove useful in guiding between upfront surgery and gene assay testing or neoadjuvant chemotherapy in this group of patients.

Feasibility of Omitting Sentinel Lymph Node Biopsy in an Under-screened Cohort of Breast Cancer Patients With a Premastectomy Diagnosis of Ductal Carcinoma In Situ.

BACKGROUND: Nodal involvement in ductal carcinoma in situ (DCIS) is rare. In patients with DCIS diagnosis prior to mastectomy, a sentinel lymph node biopsy (SLNB) is usually performed during mastectomy, to avoid the risk of reoperation and the non-identification of SLN subsequently, should there be an upgrade to invasive cancer. We aimed to study the feasibility of omitting SLNB in an under-screened cohort, with mostly symptomatic patients and DCIS diagnosis before mastectomy, by determining the upgrade rate to invasive cancer/ DCIS microinvasion (DCISM) and its associated risk factors. METHODS: Patients with pure DCIS diagnosis premastectomy were reviewed retrospectively. Patients with known DCISM or invasive cancer before mastectomy and bilateral cancers were excluded. Patients' demographics, radiological and pathological data premastectomy were analyzed. RESULTS: A total of 189 patients were included. The mean age was 53.8 (range: 29-85) years old. About 64.4% presented with symptoms. 36.0% and 15.3% upgraded to invasive cancer and DCISM on mastectomy respectively. Palpable tumor (P = .0036), large size on ultrasound (P = .0283), tumor seen on mammogram and ultrasound (P = .0082), ultrasound-guided biopsy (P < .0001), high-grade DCIS on biopsy (P = .0350) and no open biopsy/lumpectomy before mastectomy (P < .0001) were associated with the upgrade, with the latter factor remaining significant after multivariable analysis. Nodal involvement was 8.47% and was associated with invasive cancer (P < .0001). CONCLUSION: In a cohort who had DCIS diagnosis before mastectomy and were mostly symptomatic, the upgrade rate was 51.3%. Despite the high upgrade rate, nodal involvement remained comparable. Risk factors could select patients for omission of upfront SLNB, with a delayed SLNB planned if needed.

Conventional standard-sized bra with prosthesis or patient's bra with customized hand-knitted external prosthesis after mastectomy: Mixed-methods evaluation of patients' preferences.

INTRODUCTION: In breast cancer patients undergoing mastectomy without reconstruction, an external breast prosthesis could aid patients' recovery, improve body image and confidence by helping to regain a symmetrical chest appearance when dressed. However, external breast prosthesis preferences among Asian breast cancer patients were not widely studied. We aimed to compare patients' experience with the conventional commercially manufactured standard-sized (small, medium, large, extra-large) bra and prosthesis versus customized hand-knitted external breast prosthesis with patient's bra after unilateral mastectomy at a tertiary hospital. This is the first such study in Asian women, to our knowledge. METHODS: In this prospective study, participants used the conventional bra-prosthesis followed by the customized one consecutively, each for at least 3 months before they were administered an identical questionnaire at 3 and 6 months respectively. The questionnaire assessed the patients' experience with the prosthesis on the aspects of comfort, body image and satisfaction etc. Patients were also invited for in-depth interviews. RESULTS: Of 155 eligible patients, 148 patients participated with a response rate of 95.5%. 99 (67%) participants preferred the customized prosthesis, while 38 (25.7%) did not. 11 (7.4%) participants were undecided. Seventeen participants underwent in-depth interviews until data saturation on major qualitative themes was achieved. More patients experienced excessive sweating (p < 0.0001), greater discomfort (p = 0.0195) and higher rates of prosthesis dislodgement (p = 0.0269) with the conventional bra-prosthesis. CONCLUSION: Customized external breast prostheses could be an alternative to the conventional ones for breast cancer patients with mastectomy, with additional benefits of less sweating, more comfort and less dislodgement perceived.

Alterations to DNA methylation patterns induced by chemotherapy treatment are associated with negative impacts on the olfactory pathway.

BACKGROUND: Exposure to cytotoxic chemotherapy treatment may alter DNA methylation (DNAm) in breast cancer patients. METHODS: We performed DNAm analysis in 125 breast cancer patients with blood drawn before and after chemotherapy, using the Illumina MethylationEPIC array. DNAm changes of 588,798 individual CpGs (including 41,207 promoter regions) were evaluated using linear regression models adjusted for monocyte proportion. Gene set enrichment analyses (GSEA) were conducted to identify key Gene Ontology (GO) biological processes or Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways associated with chemotherapy. Results were validated in a separate cohort of breast cancer patients who were treated (n = 1273) and not treated (n = 872) by chemotherapy (1808 blood, 337 saliva). RESULTS: A total of 141 differentially methylated CpGs and 11 promoters were significantly associated with chemotherapy after multiple testing corrections in both the paired sample and single time point analyses. GSEA of promoter regions (pre-ranked by test statistics) identified six suppressed biological processes (p < 4.67e-8) related to sensory perception and detection of chemical stimuli, including smell perception (GO:0007606, GO:0007608, GO:0009593, GO:0050906, GO:0050907, and GO:0050911). The same six biological processes were significantly suppressed in the validation dataset (p < 9.02e-14). The KEGG pathway olfactory transduction (hsa04740) was also found to be significantly suppressed (ppaired-samples = 1.72e-9, psingle-timepoint-blood = 2.03e-15 and psingle-timepoint-saliva = 7.52e-56). CONCLUSION: The enrichment of imprinted genes within biological processes and pathways suggests a biological mechanism by which chemotherapy could affect the perception of smell.

Clinical presentations and outcomes of young women aged <40 yrs with Ductal carcinoma in situ.

INTRODUCTION: Ductal carcinoma in situ (DCIS) in young women is rare and not well studied. Since they do not qualify for mammographic screening, they are more likely to present with symptoms. Young women have also been associated with poorer outcomes, but it is unknown whether presentation mode affects outcome. We aimed to compare characteristics of DCIS patients <40 years of age presenting with symptoms versus those without, and determine whether presentation mode affects recurrence. METHODS: Pure DCIS patients aged <40 years were retrospectively analyzed. Clinical presentation, pathology and recurrence data were collected. Statistical analysis was performed to investigate the correlation of presentation mode with outcomes. RESULTS: 40 patients with 41 cases were included. The mean age at diagnosis was 32.3 years (range 17-39). 73.2% and 26.8% presented with symptoms or abnormal imaging respectively. Of the cases who presented with symptoms, 86.7%, 10.0% and 3.3% had palpable lump, nipple discharge or breast pain, respectively. The average tumor size was 22.0 mm (range 2.0-86.9) and 12.2 mm (range 3-25) for patients who presented with symptoms and non-symptomatic group, respectively. Cases presenting with symptoms were statistically associated with higher grade (p = 0.0090). On median follow-up of 85 months, there were 3 (7.3%) recurrences, which were not statistically associated with presentation mode. CONCLUSION: Young women with DCIS tend to present with symptoms, with breast lump as the commonest symptom. Symptomatic patients tend to be associated with grade III tumours, compared to non-symptomatic patients. On long-term follow-up, mode of presentation was not statistically associated with recurrence.

Can the size of chest wall recurrence after mastectomy in breast cancer patients predict the presence of systemic metastasis?

Background: One of the manifestations of recurrence after mastectomy is the presentation of chest wall lesion. However, it is unclear if the size of the chest wall recurrence (CWR) is related to the presence of simultaneous systemic metastasis in these patients. We aimed to determine if the size of the CWR could affect the outcome in these patients. Methods: Stage I-III breast cancer patients who underwent mastectomy and developed invasive ipsilateral CWR were included. Patients with bilateral mastectomy were excluded. Demographic, radiologic and pathological data were analysed between patients with CWR and simultaneous systemic metastasis versus those with isolated CWR. Results: Of the 1,619 patients treated with mastectomy, 214 (13.2%) patients developed recurrences. 57/214 (26.6%) patients had invasive ipsilateral CWR. 48 patients were analysed after exclusion of patients with missing data. Mean age at diagnosis of first cancer and at recurrence were 55.2 years (32-84 years) and 58.5 years (34-85 years) respectively. 26/48 (54.2%) had CWR with simultaneous systemic metastasis. Mean CWR size was 30.7 mm (6-121 mm) and 21.4 mm (5.3-90 mm) for the patients with simultaneous systemic metastasis and those without respectively (P=0.441). Grade (P=0.0008) and nodal status (P=0.0009) at primary diagnosis, grade (P=0.0011) and progesterone receptor (PR) status (P=0.0487) at recurrence were statistically significant for systemic metastasis in patients with CWR. Conclusions: Biologic factors such as grade of primary and recurrent cancer, PR status of recurrent cancer and nodal status at primary diagnosis, instead of CWR size, were associated with simultaneous systemic metastasis in patients with CWR.

A comparison of the outcomes of a novel technique of Mini-Incision and Self-Express (MISE) for breast abscess with the conventional techniques: a retrospective comparative cohort study.

Conventional techniques for treatment of breast abscess, such as incision and drainage (I&D) and needle aspiration, have disadvantages. The authors aimed to compare the outcomes of a novel technique of bedside mini-incision and self-express (MISE) for breast abscess with the conventional techniques. Methods: Patients with a pathologically confirmed breast abscess were retrospectively identified. Patients with mastitis, granulomatous mastitis, breast fillers with infection, ruptured abscess prior to intervention, other interventions or bilateral breast infection were excluded. Data collected included patient demographics, radiological features such as size and number of abscess, treatment modality, microbiological results and clinical outcomes. These outcomes were then compared between the patients with MISE, I&D and needle aspiration. Results: Twenty-one patients were included. The mean age was 31.5 years old (range: 18-48). Mean abscess size was 57.4 mm (range: 24-126). 5 (23.8%), 11 (52.4%) and 5 (23.8%) had MISE, needle aspiration and I&D, respectively. Average duration of antibiotics was 1.8, 3.9 and 2.6 weeks for MISE, needle aspiration and I&D groups, respectively, which was statistically significant after adjusting for confounders (P=0.024). Mean duration of recovery was 2.8, 7.8 and 6.2 weeks for the MISE, needle aspiration and I&D groups, respectively (P=0.027), after adjusting for confounders. Conclusion: MISE, in suitable patients, results in shorter recovery time and lesser antibiotics usage, compared with the conventional techniques.

An unusual site for breast clip migration: A case report.

Clip migration following breast biopsy is a known complication. However, the migrated clip is usually found within the breast. We describe a rare case of delayed clip migration to the skin, following a magnetic resonance guided biopsy of the breast, highlighting its natural history of presentation and its treatment.

Axillary management of breast cancer patients with isolated chest wall recurrence after mastectomy.

Background: National Comprehensive Cancer Network (NCCN) guidelines on the axillary management of breast cancer patients with isolated chest wall recurrence after mastectomy are unclear. Though sentinel lymph node biopsy (SLNB) is possible and may be considered, there is limited data on its usefulness. We aimed to determine if axillary restaging surgery was required in this cohort of patients who developed operable isolated chest wall recurrences after mastectomy. Methods: Breast cancer patients treated at a tertiary institution from 1st September 2005 to 31st October 2017 and developed isolated chest wall invasive recurrences after mastectomy were retrospectively reviewed. We excluded patients with bilateral cancers, concurrent regional or distant metastases, patients without surgery for their chest wall recurrences and patients who were lost to follow-up. The demographics, pathological data and second recurrences were collected from a prospectively maintained database and compared between patients with axillary lymph node dissection (ALND), SLNB and no axillary operation. Results: Of the 1,841 patients who underwent mastectomy, 26 (1.4%) patients developed isolated chest wall recurrences. Twenty two eligible patients were analysed. The mean age at diagnosis of the recurrence was 54.7 years (range, 37-84 years). 1, 2 and 19 patients had ALND, SLNB and no axillary operation respectively. On mean follow-up of 38.3 months, no axillary recurrences were noted. Conclusions: In breast cancer patients with isolated chest wall recurrences after mastectomy, axillary restaging surgery can be safely omitted with no increased axillary recurrences on medium term follow-up. This finding could refine existing guidelines in the management of the axilla for patients with chest wall recurrences after mastectomy.

Oncologic outcomes in breast cancer patients with metastatic nodes and pathological nodal response following neoadjuvant chemotherapy without axillary dissection: a literature review.

Background and Objective: With promising nodal pathological complete response (pCR) after neoadjuvant chemotherapy, the role of axillary lymph node dissection (ALND) was questioned. While there is much data on the accuracy of axillary staging after neoadjuvant chemotherapy to predict nodal pCR, limited data on the oncological safety of omitting ALND exists. We aim to review the oncological safety of omitting ALND in patients with initially metastatic nodes achieving nodal pCR, based on axillary staging, following neoadjuvant chemotherapy. Methods: A PubMed search of relevant articles from 1st January 2013 to 15th September 2022 was performed. Studies with duplication of patients, ALND only, no oncological details, initially N0 patients only and patients without nodal pCR were excluded. Key Content and Findings: Fifteen studies with 1,515 eligible patients (range, 29-242 patients) were analysed. There was heterogeneity of patients among the included studies and patients had varying TN staging, making selection criteria for omission of ALND inconclusive. Sentinel lymph node biopsy (SLNB) was the most studied mode of axillary staging in 1,416 (93.5%) patients, though 35.7% had <3 SLN harvested. On average median follow-up of 52.8 months (range, 9-110 months), axillary recurrence ranged from 0% to 3.4%. There was limited data on survival outcomes. Conclusions: In node positive breast cancer patients who achieved nodal pCR after neoadjuvant chemotherapy, the axillary recurrence rate was low without ALND. However, survival data was limited. The selection criteria and ideal axillary staging technique for patients, who are suitable for axillary preservation, are unclear. More prospective studies with longer follow-up, providing survival data, are needed.

Is Metastatic Staging Needed for All Patients with Synchronous Bilateral Breast Cancers?

BACKGROUND: Patients with bilateral breast cancers are uncommon and are associated with a poorer prognosis. While metastatic staging guidelines in patients with unilateral cancer were established, the indication of metastatic staging in patients with bilateral breast cancers is unclear. We aimed to determine which patients with synchronous bilateral breast cancers require metastatic staging at diagnosis. This is the first such reported study, to the best of our knowledge. METHODS: A retrospective review of newly diagnosed synchronous bilateral invasive breast cancer patients at our institution was performed. We excluded patients with malignant phyllodes or no metastatic staging. Patients' demographics and pathological and staging results were analysed to determine the group of bilateral breast cancer patients who required metastatic staging. RESULTS: A total of 92 patients with synchronous bilateral invasive cancers were included. The mean age was 58 years old, and 64.1% had bilateral invasive ductal carcinoma. 23.9% had systemic metastasis. Nodal status was statistically significant for systemic metastasis on staging (p = 0.0081), with only three patients (3.3%) having negative nodal status and positive metastatic staging. These three patients, however, showed symptoms of distant metastasis. 92.3% of patients with negative nodes also had negative metastatic staging. Using negative nodal status as a guide avoided metastatic staging in 40.4% of all patients. CONCLUSIONS: Negative nodal status was the most predictive factor for no systemic metastasis on staging in patients with synchronous bilateral invasive breast cancers. Hence, metastatic staging could be reserved for patients with symptoms of systemic metastasis and/or metastatic nodes. This finding could be validated in larger studies.

Patterns of breast cancer second recurrences in patients after mastectomy.

INTRODUCTION: Little is known about second recurrences in breast cancer patients, especially in patients with mastectomy. We aimed to determine the risk factors, prevalence and patterns of second recurrence in mastectomy patients after first recurrence. METHODS: Stage I-III breast cancer patients treated at a tertiary institution from 1st September 2005 to 31st October 2017 and developed first and second recurrences after mastectomy were retrospectively reviewed. We excluded patients with bilateral cancers and patients who were lost to follow-up. The demographics, pathological and recurrence data were collected from a prospectively maintained database and analysed. RESULTS: Of the 1619 mastectomy patients, 214 (13.2%) patients developed recurrences at a mean 39.9 months from primary cancer diagnosis. 23, 8 and 183 had isolated chest wall recurrences (CWR), regional and systemic metastases, respectively. Excluding 2 CWR patients without surgery, second recurrences occurred in 3/21 (14.3%) and 3/8 (37.5%) in patients with CWR and regional metastasis at 27.7 months (range: 5-42) and 32 months (range: 18-40), respectively. In both groups, systemic metastasis as second recurrence occurred within 2 years after first recurrence, whilst locoregional second recurrences occurred later. No risk factors for second recurrence were identified. CONCLUSION: In patients with mastectomy, second recurrences occurred in 20.7% of patients with treated locoregional first recurrence, with no risk factors identified. Systemic metastases manifesting as second recurrence occurred in the first 2 years after first recurrence. Continued clinical surveillance and restaging patients in the first 2 years after first locoregional recurrence may enable early prognostication and treatment with the newer metastatic drugs.

Mammography screening is associated with more favourable breast cancer tumour characteristics and better overall survival: case-only analysis of 3739 Asian breast cancer patients.

BACKGROUND: Early detection of breast cancer (BC) through mammography screening (MAM) is known to reduce mortality. We examined the differential effect that mammography has on BC characteristics and overall survival and the sociodemographic determinants of MAM utilization in a multi-ethnic Asian population. METHODS: This study included 3739 BC patients from the Singapore Breast Cancer Cohort (2010-2018). Self-reported sociodemographic characteristics were collected using a structured questionnaire. Clinical data were obtained through medical records. Patients were classified as screeners (last screening mammogram ≤ 2 years before diagnosis), non-screeners (aware but did not attend or last screen > 2years), and those unaware of MAM. Associations between MAM behaviour (MB) and sociodemographic factors and MB and tumour characteristics were examined using multinomial regression. Ten-year overall survival was modelled using Cox regression. RESULTS: Patients unaware of screening were more likely diagnosed with late stage (ORstage III vs stage I (Ref) [95% CI]: 4.94 [3.45-7.07], p < 0.001), high grade (ORpoorly vs well-differentiated (reference): 1.53 [1.06-2.20], p = 0.022), nodal-positive, large size (OR>5cm vs ≤2cm (reference): 5.06 [3.10-8.25], p < 0.001), and HER2-positive tumours (ORHER2-negative vs HER2-positive (reference): 0.72 [0.53-0.97], p = 0.028). Similar trends were observed between screeners and non-screeners with smaller effect sizes. Overall survival was significantly shorter than screeners in the both groups (HRnon-screeners: 1.89 [1.22-2.94], p = 0.005; HRunaware: 2.90 [1.69-4.98], p < 0.001). Non-screeners and those unaware were less health conscious, older, of Malay ethnicity, less highly educated, of lower socioeconomic status, more frequently ever smokers, and less physically active. Among screeners, there were more reported personal histories of benign breast surgeries or gynaecological conditions and positive family history of breast cancer. CONCLUSIONS: Mammography attendance is associated with more favourable BC characteristics and overall survival. Disparities in the utility of MAM services suggest that different strategies may be needed to improve MAM uptake.

Determining the benefit of neoadjuvant chemotherapy in reduction of axillary dissection rates in Z0011 trial cohort with high nodal burden.

Background: In breast cancer patients fulfilling the Z0011 trial criteria, axillary lymph node dissection (ALND) is reserved for patients with a high nodal burden of ≥3 metastatic nodes. In this group of patients, to avoid an ALND, neoadjuvant chemotherapy (NACT) could be given instead to achieve nodal pathological complete response (pCR). However, the benefit of NACT in achieving nodal pCR and avoiding ALND in this group of patients is unknown. We aimed to determine the nodal pCR rate in this group of patients who otherwise would have needed an ALND. Methods: cT1-2N0 breast cancer patients, with histologically proven nodal metastasis, who underwent NACT were identified from a prospectively maintained database. The sonographic criteria of ≥3 abnormal nodes, which has been reported as highly predictive of high nodal burden, was then used to identify the high nodal burden group. Nodal pCR was determined based on the ALND following NACT. Results: Twenty-four patients with high nodal burden were identified. Mean age was 55.2 years. 91.7% had invasive ductal carcinoma and 29.2% had grade III cancer. 54.2% achieved nodal pCR which was associated with ypT (P=0.006). Nodal pCR was 75%, 70% and 30% in the triple negative, human epidermal growth factor receptor2 (HER2) positive and ER/PR+HER2- tumors, respectively. Conclusions: In the postulated T1-2 breast cancer patients with high nodal burden, needing an upfront ALND, NACT could result in nodal pCR of 54.2%, with higher pCR in certain subtypes. Hence, to minimize ALND risk, NACT should be offered in this high nodal burden group.

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.