21-gene expression assay and clinical outcomes of premenopausal patients with hormone receptor-positive breast cancer.

The prognostic role of the recurrence score (RS) based on the 21-gene expression assay in premenopausal women is not well delineated, and we investigated the association of outcomes and the RS in premenopausal patients who had 21-gene expression assay at Asan Medical Center, Seoul, Korea, between June 2005 and July 2018. Invasive breast cancer-free survival (IBCFS) by STEEP version 2.0 was compared according to the RS and clinical risk factors. A total of 554 patients were included in our study and 116 patients (20.9%) had age <40 years, 238 patients (43.0%) had luminal B subtype (Ki67 ≥ 20%), and 83 patients (15.0%) had RS >25. All patients received adjuvant tamoxifen ± chemotherapy. Overall, patients with RS >25 showed trend toward worse IBCFS from multivariable analysis (adjusted HR 1.89 [95% CI: 0.95-3.73], P = .069). When comparing outcomes according to age and luminal subtypes, patients with luminal B subtype and age <40 years (n = 60) showed significantly worse outcomes compared to the others (luminal A or luminal B + age ≥40 years, n = 494; adjusted HR 2.95 [95% CI: 1.49-5.82], log-rank P < .001). Among patients with luminal B subtype and age <40 years, there was no significant association observed between IBCFS and the RS (log-rank P = .51). In conclusion, while RS >25 showed association with poor outcomes in premenopausal women, it may have less prognostic significance among those with luminal B subtype and age <40 years.

Characterization of HER2-low breast cancer in young women with germline BRCA1/2 pathogenetic variants: Results of a large international retrospective cohort study.

BACKGROUND: Breast cancer (BC) in women aged ≤40 years carrying germline pathogenetic variants (PVs) in BRCA1/2 genes is infrequent but often associated with aggressive features. Human epidermal growth factor receptor 2 (HER2)-low-expressing BC has recently emerged as a novel therapeutic target but has not been characterized in this rare patient subset. METHODS: Women aged ≤40 years with newly diagnosed early-stage HER2-negative BC (HER2-0 and HER2-low) and germline BRCA1/2 PVs from 78 health care centers worldwide were retrospectively included. Chi-square test and Student t-test were used to describe variable distribution between HER2-0 and HER2-low. Associations with HER2-low status were assessed with logistic regression. Kaplan-Meier method and Cox regression analysis were used to assess disease-free survival (DFS) and overall survival. Statistical significance was considered for p ≤ .05. RESULTS: Of 3547 included patients, 32.3% had HER2-low BC, representing 46.3% of hormone receptor-positive and 21.3% of triple-negative (TN) tumors. HER2-low vs. HER2-0 BC were more often of grade 1/2 (p < .001), hormone receptor-positive (p < .001), and node-positive (p = .003). BRCA2 PVs were more often associated with HER2-low than BRCA1 PVs (p < .001). HER2-low versus HER2-0 showed better DFS (hazard ratio [HR], 0.86; 95% CI, 0.76-0.97) in the overall population and more favorable DFS (HR, 0.78; 95% CI, 0.64-0.95) and overall survival (HR, 0.65; 95% CI, 0.46-0.93) in the TN subgroup. Luminal A-like tumors in HER2-low (p = .014) and TN and luminal A-like in HER2-0 (p = .019) showed the worst DFS. CONCLUSIONS: In young patients with HER2-negative BC and germline BRCA1/2 PVs, HER2-low disease was less frequent than expected and more frequently linked to BRCA2 PVs and associated with luminal-like disease. HER2-low status was associated with a modestly improved prognosis.

Long-term outcome in patients with nodal-positive breast cancer treated with sentinel lymph node biopsy alone after neoadjuvant chemotherapy.

PURPOSE: Sentinel lymph node biopsy (SLNB) has yet to be accepted as the standard staging procedure in node positive (cN1) breast cancer patients who had clinical complete response in the axilla (cN0) following neoadjuvant chemotherapy (NAC), due to the presumed high false negative rate associated with SLNB in such scenario. This study aimed to determine whether there is a significant difference in the axillary recurrence rate (ARR) and long-term survival in this group of patients, receiving SLNB alone versus axillary lymph node dissection (ALND). METHODS: A retrospective cohort of cN1 patients who were rendered cN0 by NAC from January 2014 to December 2018 were identified from the Asan Medical Center database. Patients' characteristics and outcomes were collected and analyzed. RESULTS: 902 cN1 patients treated with NAC and turned cN0 were identified. 477 (52.9%) patients achieved complete pathological response in the axilla (ypN0). At a median follow up of 65 months, ARR was 3.2% in the SLNB only group and 1.8% in the ALND group (p = 0.398). DFS and OS were significantly worse in patients with ALND as compared to patients with SLNB only (p = 0.011 and 0.047, respectively). We noted more patients in the ALND group had T3-4 tumor. In the subgroup analysis, we showed that in the T1-2 subgroup (n = 377), there was no statistically significant difference in DFS and OS (p = 0.242 and 0.671, respectively) between SLNB only and ALND group. CONCLUSION: Our findings suggest that cN1 patients who were converted to ypN0 following NAC may be safely treated with SLNB only.

Characteristics and risk factors of axillary lymph node metastasis of microinvasive breast cancer.

PURPOSE: To select patients who would benefit most from sentinel lymph node biopsy (SLNB) by investigating the characteristics and risk factors of axillary lymph node metastasis (ALNM) in microinvasive breast cancer (MIBC). METHODS: This retrospective study included 1688 patients with MIBC who underwent breast surgery with axillary staging at the Asan Medical Center from 1995 to 2020. RESULTS: Most patients underwent SLNB alone (83.5%). Seventy (4.1%) patients were node-positive, and the majority had positive lymph nodes < 10 mm, with micro-metastases occurring frequently (n = 37; 55%). Node-positive patients underwent total mastectomy and axillary lymph node dissection (ALND) more than breast-conserving surgery (BCS) and SLNB compared with node-negative patients (p < 0.001). In the multivariate analysis, independent predictors of ALNM included young age [odds ratio (OR) 0.959; 95% confidence interval (CI) 0.927-0.993; p = 0.019], ALND (OR 11.486; 95% CI 5.767-22.877; p < 0.001), number of lymph nodes harvested (≥ 5) (OR 3.184; 95% CI 1.555-6.522; p < 0.001), lymphovascular invasion (OR 6.831; 95% CI 2.386-19.557; p < 0.001), presence of multiple microinvasion foci (OR 2.771; 95% CI 1.329-5.779; p = 0.007), prominent lymph nodes in preoperative imaging (OR 2.675; 95% CI 1.362-5.253; p = 0.004), and hormone receptor positivity (OR 2.491; 95% CI 1.230-5.046; p = 0.011). CONCLUSION: Low ALNM rate (4.1%) suggests that routine SLNB for patients with MIBC is unnecessary but can be valuable for patients with specific risk factors. Ongoing trials for omitting SLNB in early breast cancer, and further subanalyses focusing on rare populations with MIBC are necessary.

Comparison of long-term oncological outcomes after central lumpectomy versus nipple-sparing breast-conserving surgery for centrally located breast cancer: a propensity score-matched study.

PURPOSE: To compare the oncological safety of nipple-sparing breast-conserving surgery (BCS) versus central lumpectomy for centrally located breast cancer (CLBC). METHODS: Patients who underwent BCS for CLBC at Asan Medical Center from 2007 to 2018 were reviewed retrospectively. The oncological outcomes of nipple-sparing BCS (NS-BCS) and central lumpectomy were compared using univariate and multivariate Cox regression analyses and compared again after 1:1 propensity score matching (PSM). RESULTS: The study included 306 patients who underwent NS-BCS and 106 patients who underwent central lumpectomy (median follow-up: 111 months). On multivariate analysis, central lumpectomy had a lower risk of local recurrence compared to NS-BCS, albeit without statistical significance (HR 0.14, 95% CI 0.02-1.24; p = 0.077). There was no significant difference in the risk of death (HR 0.14, 95% CI 0.01-1.68, p = 0.12). After PSM, each group had 106 patients. The 5-year and 10-year local recurrence-free survival rates were 94.2% and 92.9% for NS-BCS, and 99.1% and 99.1% for central lumpectomy, respectively (p = 0.031). There were no significant differences in overall survival, regional recurrence-free survival, or distant recurrence-free survival. Fifteen patients (4.9%) who underwent NS-BCS had ipsilateral breast tumor recurrence (IBTR), of which 40% were in the nipple-areolar complex and previous surgical sites. One patient (0.9%) who underwent central lumpectomy experienced an IBTR in a different quadrant. CONCLUSION: NS-BCS showed more local recurrence than central lumpectomy. When deciding whether to spare the nipple during BCS in CLBC, patients should be sufficiently informed about the risk of IBTR.

Use of a commercial artificial intelligence-based mammography analysis software for improving breast ultrasound interpretations.

OBJECTIVES: To evaluate the use of a commercial artificial intelligence (AI)-based mammography analysis software for improving the interpretations of breast ultrasound (US)-detected lesions. METHODS: A retrospective analysis was performed on 1109 breasts that underwent both mammography and US-guided breast biopsy. The AI software processed mammograms and provided an AI score ranging from 0 to 100 for each breast, indicating the likelihood of malignancy. The performance of the AI score in differentiating mammograms with benign outcomes from those revealing cancers following US-guided breast biopsy was evaluated. In addition, prediction models for benign outcomes were constructed based on clinical and imaging characteristics with and without AI scores, using logistic regression analysis. RESULTS: The AI software had an area under the receiver operating characteristics curve (AUROC) of 0.79 (95% CI, 0.79-0.82) in differentiating between benign and cancer cases. The prediction models that did not include AI scores (non-AI model), only used AI scores (AI-only model), and included AI scores (integrated model) had AUROCs of 0.79 (95% CI, 0.75-0.83), 0.78 (95% CI, 0.74-0.82), and 0.85 (95% CI, 0.81-0.88) in the development cohort, and 0.75 (95% CI, 0.68-0.81), 0.82 (95% CI, 0.76-0.88), and 0.84 (95% CI, 0.79-0.90) in the validation cohort, respectively. The integrated model outperformed the non-AI model in the development and validation cohorts (p < 0.001 for both). CONCLUSION: The commercial AI-based mammography analysis software could be a valuable adjunct to clinical decision-making for managing US-detected breast lesions. CLINICAL RELEVANCE STATEMENT: The commercial AI-based mammography analysis software could potentially reduce unnecessary biopsies and improve patient outcomes. KEY POINTS: • Breast US has high rates of false-positive interpretations. • A commercial AI-based mammography analysis software could distinguish mammograms having benign outcomes from those revealing cancers after US-guided breast biopsy. • A commercial AI-based mammography analysis software may improve interpretations for breast US-detected lesions.

Ovarian Suppression: Early Menopause and Late Effects.

OPINION STATEMENT: Around 90% of breast tumours are diagnosed in the early stage, with approximately 70% being hormone receptor-positive. The cornerstone of adjuvant therapy for early-stage hormone receptor-positive breast cancer is endocrine therapy, tailored according to disease stage, biological characteristics of the tumour, patient's comorbidities, preferences and age. In premenopausal patients with hormone receptor-positive breast cancer, ovarian function suppression is a key component of the adjuvant endocrine treatment in combination with an aromatase inhibitor or tamoxifen. Moreover, it can be used during chemotherapy as a standard strategy for ovarian function preservation in all breast cancer subtypes. In the metastatic setting, ovarian function suppression should be used in all premenopausal patients with hormone receptor-positive breast cancer to achieve a post-menopausal status. Despite its efficacy, ovarian function suppression may lead to several side effects that can have a major negative impact on patients' quality of life if not properly managed (e.g. hot flashes, depression, cognitive impairment, osteoporosis, sexual dysfunction, weight gain). A deep knowledge of the side effects of ovarian function suppression is necessary for clinicians. A correct counselling in this regard and proactive management should be considered a fundamental part of survivorship care to improve treatment adherence and patients' quality of life.

Pregnancy After Breast Cancer in Young BRCA Carriers: An International Hospital-Based Cohort Study.

Importance: Young women with breast cancer who have germline pathogenic variants in BRCA1 or BRCA2 face unique challenges regarding fertility. Previous studies demonstrating the feasibility and safety of pregnancy in breast cancer survivors included limited data regarding BRCA carriers. Objective: To investigate cumulative incidence of pregnancy and disease-free survival in young women who are BRCA carriers. Design, Setting, and Participants: International, multicenter, hospital-based, retrospective cohort study conducted at 78 participating centers worldwide. The study included female participants diagnosed with invasive breast cancer at age 40 years or younger between January 2000 and December 2020 carrying germline pathogenic variants in BRCA1 and/or BRCA2. Last delivery was October 7, 2022; last follow-up was February 20, 2023. Exposure: Pregnancy after breast cancer. Main Outcomes and Measures: Primary end points were cumulative incidence of pregnancy after breast cancer and disease-free survival. Secondary end points were breast cancer-specific survival, overall survival, pregnancy, and fetal and obstetric outcomes. Results: Of 4732 BRCA carriers included, 659 had at least 1 pregnancy after breast cancer and 4073 did not. Median age at diagnosis in the overall cohort was 35 years (IQR, 31-38 years). Cumulative incidence of pregnancy at 10 years was 22% (95% CI, 21%-24%), with a median time from breast cancer diagnosis to conception of 3.5 years (IQR, 2.2-5.3 years). Among the 659 patients who had a pregnancy, 45 (6.9%) and 63 (9.7%) had an induced abortion or a miscarriage, respectively. Of the 517 patients (79.7%) with a completed pregnancy, 406 (91.0%) delivered at term (≥37 weeks) and 54 (10.4%) had twins. Among the 470 infants born with known information on pregnancy complications, 4 (0.9%) had documented congenital anomalies. Median follow-up was 7.8 years (IQR, 4.5-12.6 years). No significant difference in disease-free survival was observed between patients with or without a pregnancy after breast cancer (adjusted hazard ratio, 0.99; 95% CI, 0.81-1.20). Patients who had a pregnancy had significantly better breast cancer-specific survival and overall survival. Conclusions and Relevance: In this global study, 1 in 5 young BRCA carriers conceived within 10 years after breast cancer diagnosis. Pregnancy following breast cancer in BRCA carriers was not associated with decreased disease-free survival. Trial Registration: ClinicalTrials.gov Identifier: NCT03673306.

Clinical significance of microinvasive breast cancer across the different subtypes and human epidermal growth factor receptor 2 expression levels.

PURPOSE: The clinical behavior, prognosis, and management of microinvasive breast cancer (MiBC) is controversial. We aimed to clarify its significance across different subtypes and the role of human epidermal growth factor receptor 2 (HER2) expression in MiBC. METHODS: We analyzed 1530 patients with T1mi (tumor size ≤ 0.1 cm), node-negative breast cancer who underwent breast conserving surgery or total mastectomy between 2001 and 2020 at the Asan Medical Center (AMC). RESULTS: When divided into four subtypes, hormone receptor (HR)+/HER2-, HR+ /HER2+ , HR-/HER2+ , and HR-/HER2-, HR-/HER2+ had the highest prevalence rate of 38.5% in MiBC patients. In a median follow-up period of 74 months (0-271 months), 103 (6.7%) patients had recurrent tumor, and 95 (6.2%) had local recurrence. Disease-free survival (DFS) and local recurrence-free survival (LRFS) were worst in the HR-/HER2+ group. The five-year DFS for the HR-/HER2+ group was 92.2%, while it was 97.1% for the HR+/HER2- group (p = 0.024 The five-year LRFS for HER2- patients were better than that of HER2+ MiBC patients, which were 97.1 and 93.8%, respectively (p = 0.010). Univariate and multivariate Cox regression analyses showed that the HR-/HER2+ group had relatively higher risk of recurrence compared to the HR+/HER2- group (hazard ratio [HR] = 2.332, 95% confidence interval [CI] 1.412-3.852, p = 0.001 unadjusted; HR = 3.346, 95% CI 1.408-7.953, p = 0.006 adjusted). CONCLUSION: HER2 overexpression was significantly associated with adverse clinicopathologic parameters and increased local recurrence risk in MiBC. Therefore, more understanding of the clinical behavior of HER2 in MiBC will enable tailoring of adjuvant therapy for these patients.

Survival After Breast-Conserving Surgery Compared with that After Mastectomy in Breast Cancer Patients Receiving Neoadjuvant Chemotherapy.

BACKGROUND: Breast-conserving surgery (BCS) plus radiotherapy (BCS + RT) has been shown to improve survival compared with mastectomy in patients with early breast cancer; however, whether this superiority is maintained in breast cancer patients receiving neoadjuvant chemotherapy (NCT) is unclear. We evaluated and compared the survival outcomes after BCS + RT and mastectomy in Korean women with breast cancer treated with NCT. METHODS: We evaluated 1641 patients who received NCT before surgery (BCS or mastectomy). We performed propensity score matching to minimize potential bias due to factors other than the surgical method and compared the 5-year, disease-free survival (DFS), distant metastasis-free survival (DMFS), and overall survival (OS) rates before and after exact matching. RESULTS: Among the 1641 patients, 839 (51.1%) underwent BCS + RT and 802 (48.9%) underwent mastectomy. Patients who underwent mastectomy had larger tumors and more frequently had positive nodes. For BCS+RT and mastectomy, the unadjusted 5-year DFS, 5-year DMFS, and 5-year OS rates were 87.0% and 73.1%, 89.5% and 77.0%, and 91.8% and 81.0%, respectively (all p < 0.05 = 0.000). After PSM, 5-year DFS, 5-year DMFS, and 5-year OS rates for BCS + RT and mastectomy were 87.6% and 69.1%, 89.7% and 76.0%, and 89.1% and 75.7%, respectively (all p < 0.05). In both unadjusted and adjusted analyses accounting for various confounding factors, BCS + RT was significantly associated with improved DFS (p < 0.05), DMFS (p < 0.05), and OS (p < 0.05) rates compared with mastectomy. CONCLUSIONS: BCS + RT does not impair DFS and OS in patients treated with NCT. Tumor biology and treatment response are significant prognostic indicators. Our results suggest that BCS + RT may be preferred in most breast cancer patients when both BCS and mastectomy are suitable.

Improving mammography interpretation for both novice and experienced readers: a comparative study of two commercial artificial intelligence software.

OBJECTIVES: To evaluate the improvement of mammography interpretation for novice and experienced radiologists assisted by two commercial AI software. METHODS: We compared the performance of two AI software (AI-1 and AI-2) in two experienced and two novice readers for 200 mammographic examinations (80 cancer cases). Two reading sessions were conducted within 4 weeks. The readers rated the likelihood of malignancy (range, 1-7) and the percentage probability of malignancy (range, 0-100%), with and without AI assistance. Differences in AUROC, sensitivity, and specificity were analyzed. RESULTS: Mean AUROC increased in both novice (0.86 to 0.90 with AI-1 [p = 0.005]; 0.91 with AI-2 [p < 0.001]) and experienced readers (0.87 to 0.92 with AI-1 [p < 0.001]; 0.90 with AI-2 [p = 0.004]). Sensitivities increased from 81.3 to 88.8% with AI-1 (p = 0.027) and to 91.3% with AI-2 (p = 0.005) in novice readers, and from 81.9 to 90.6% with AI-1 (p = 0.001) and to 87.5% with AI-2 (p = 0.016) in experienced readers. Specificity did not decrease significantly in both novice (p > 0.999, both) and experienced readers (p > 0.999 with AI-1 and 0.282 with AI-2). There was no significant difference in the performance change depending on the type of AI software (p > 0.999). CONCLUSION: Commercial AI software improved the diagnostic performance of both novice and experienced readers. The type of AI software used did not significantly impact performance changes. Further validation with a larger number of cases and readers is needed. CLINICAL RELEVANCE STATEMENT: Commercial AI software effectively aided mammography interpretation irrespective of the experience level of human readers. KEY POINTS: • Mammography interpretation remains challenging and is subject to a wide range of interobserver variability. • In this multi-reader study, two commercial AI software improved the sensitivity of mammography interpretation by both novice and experienced readers. The type of AI software used did not significantly impact performance changes. • Commercial AI software may effectively support mammography interpretation irrespective of the experience level of human readers.

A Propensity Score-matched Analysis of Long-term Oncologic Outcomes After Nipple-sparing Versus Conventional Mastectomy for Locally Advanced Breast Cancer.

OBJECTIVES: To compare the long-term oncologic outcomes of nipple-sparing mastectomy (NSM) with those of conventional mastectomy (CM) in patients with locally advanced breast cancer (LABC) receiving neoadjuvant chemotherapy (NACT). SUMMARY OF BACKGROUND DATA: NSM has been increasingly implemented in patients with breast cancer. However, oncologic efficacy of NSM in patients with LABC has not been sufficiently demonstrated. METHODS: The study group comprised 850 patients with clinical stage IIB to IIIC breast cancer who underwent NACT followed by either NSM and immediate breast reconstruction or CM alone. After propensity score-matching, 418 patients were included in the analysis. Local recurrence-free survival, disease-free survival (DFS), distant metastasis-free survival, and overall survival (OS) rates were calculated using the Kaplan-Meier method and compared using log-rank tests between the NSM and CM groups. RESULTS: After matching, the mean follow-up period was 70 ± 25 months for the NSM group and 74 ± 27 months for the CM group ( P = 0.181). There were no significant differences between the groups in terms of 6-year local recurrence-free survival (91.6% vs. 95.8%; P = 0.239), DFS (70.5% vs. 73.4%; P = 0.583), distant metastasis-free survival (79.8% vs. 77.4%; P = 0.320), or OS (87.6% vs. 84.8%; P = 0.465) rates. Additionally, we identified 30 patients in the NSM group who initially presented with tumor extension in the subareolar area; the nipple-areola complex was successfully preserved after NACT, and no recurrence at the nipple was observed in these patients. CONCLUSIONS: In this matched control study, we demonstrated comparable long-term oncologic outcomes between NSM with immediate reconstruction and CM alone after NACT for LABC. In patients who had tumors extending to the subareolar area before NACT, NSM can be tried if tumor involvement of the nipple-areola complex appears resolved on imaging studies after chemotherapy.

Surgical Treatment After Neoadjuvant Systemic Therapy in Young Women With Breast Cancer: Results From a Prospective Cohort Study.

OBJECTIVE: We aimed to investigate eligibility for breast conserving surgery (BCS) pre- and post-neoadjuvant systemic therapy (NST), and trends in the surgical treatment of young breast cancer patients. BACKGROUND: Young women with breast cancer are more likely to present with larger tumors and aggressive phenotypes, and may benefit from NST. Little is known about how response to NST influences surgical decisions in young women. METHODS: The Young Women's Breast Cancer Study, a multicenter prospective cohort of women diagnosed with breast cancer at age ≤40, enrolled 1302 patients from 2006 to 2016. Disease characteristics, surgical recommendations, and reasons for choosing mastectomy among BCS-eligible patients were obtained through the medical record. Trends in use of NST, rate of clinical and pathologic complete response, and surgery were also assessed. RESULTS: Of 1117 women with unilateral stage I-III breast cancer, 315 (28%) received NST. Pre-NST, 26% were BCS eligible, 17% were borderline eligible, and 55% were ineligible. After NST, BCS eligibility increased from 26% to 42% (P < 0.0001). Among BCS-eligible patients after NST (n = 133), 41% chose mastectomy with reasons being patient preference (53%), BRCA or TP53 mutation (35%), and family history (5%). From 2006 to 2016, the rates of NST (P = 0.0012), clinical complete response (P < 0.0001), and bilateral mastectomy (P < 0.0001) increased, but the rate of BCS did not increase (P = 0.34). CONCLUSION: While the proportion of young women eligible for BCS increased after NST, many patients chose mastectomy, suggesting that surgical decisions are often driven by factors beyond extent of disease and treatment response.

Chemotherapy for ipsilateral breast tumor recurrence: a propensity score-matching study.

PURPOSE: We evaluated the benefit of chemotherapy in patients with ipsilateral breast tumor recurrence (IBTR) by comparing the survival outcomes between the chemotherapy and no chemotherapy groups, using propensity score matching (PSM), and analyze the survival outcomes stratified by hormone receptor status of IBTR. METHODS: We retrospectively analyzed patients who developed invasive IBTR after undergoing breast-conserving surgery at our institution between 1990 and 2013. A 1:1 PSM analysis was performed to compare the survival rates between the two study groups; additional analysis stratified by hormone receptor status was performed. The Kaplan-Meier method and Cox proportional hazards model were used to compare the second recurrence-free survival (RFS), distant metastasis-free survival (DMFS), and overall survival (OS) rates between the two groups. RESULTS: The 217 IBTR patients had a median follow-up of 125.3 months. After PSM, patients without chemotherapy and with chemotherapy (n = 35 in both groups) were included. No significant differences were observed in the 10-year second RFS [50.2% without chemotherapy vs. 39.8% with chemotherapy, hazard ratio (HR) 0.95, 95% confidence interval (CI) 0.50-1.80], DMFS (85.4% vs. 70.3%, HR 1.51, 95% CI 0.66-3.44), and OS (81.6% vs. 68.6%, HR 1.73, 95% CI 0.76-3.90) rates between the two groups. Analyses stratified by hormone receptor status showed similar findings: no significant differences were observed in the second RFS, DMFS, and OS rates between the two groups in both hormone receptor-positive and -negative groups. CONCLUSION: Chemotherapy had no impact in the long-term survival outcomes of IBTR patients regardless of the hormone receptor status.

Oncologic outcomes of immediate breast reconstruction in young women with breast cancer receiving neoadjuvant chemotherapy.

BACKGROUND: Oncologic safety of postmastectomy breast reconstruction in young women with breast cancer is not well-defined, especially in the setting of neoadjuvant chemotherapy (NACT). We retrospectively compared the oncologic outcomes following nipple-sparing (NSM)/skin-sparing mastectomy (SSM) with immediate breast reconstruction (IBR) and conventional mastectomy (CM) alone in young breast cancer patients after NACT. METHODS: A total of 1266 women with primary breast cancer who underwent NACT followed by total mastectomy with or without IBR were reviewed. Of these, only young patients (age ≤ 40 years at diagnosis) were included in the outcome analysis (n = 375). After propensity score-matching by clinical T and N stage, molecular subtype, response to NACT, and adjuvant radiotherapy status, 228 patients were 1:1 matched, comprising balanced IBR group (with NSM/SSM) and CM-alone group. RESULTS: The 5-year locoregional recurrence-free, disease-free, distant metastasis (DM)-free, and breast cancer-specific survival (BCSS) rates for the entire cohort of young patients were 83.4%, 65.3%, 71.7%, and 85.4%, respectively. Locoregional recurrence rates between the matched groups were similar (14% vs. 15.8%; p = 0.710); however, IBR group had significantly lower DM rate (27.2% vs. 40.4%; p = 0.036) and breast cancer mortality (14.9% vs. 27.2%; p = 0.023) than CM-alone group. IBR group showed significantly improved 5-year DM-free survival (74.1% vs. 62.6%; p = 0.043) and BCSS (89.1% vs. 77.6%; p = 0.048) rates than CM-alone group. CONCLUSIONS: Our results indicated that IBR with NSM/SSM does not negatively affect long-term oncologic outcomes compared to CM alone in young women with breast cancer receiving NACT.

Breast cancer outcomes following immediate breast reconstruction with implants versus autologous flaps: a propensity score-matched study.

PURPOSE: A large proportion of patients with breast cancer who had mastectomy had undergone breast reconstruction with implants or autologous flaps. However, only a few studies have compared the breast cancer outcomes between the implant-based reconstruction (IBR) and autologous flap reconstruction (AFR). In this study, we retrospectively compared the local recurrence rates, distant metastasis rates, and survival outcomes between immediate IBR and AFR. METHODS: A total of 1530 patients with primary breast cancer who underwent IBR or AFR with nipple-/skin-sparing mastectomy were included. Patients who underwent neoadjuvant systemic therapy were excluded from the study. After propensity score matching by age at diagnosis, T stage, N stage, molecular subtype, mastectomy type, adjuvant radiotherapy status, and follow-up period, 938 patients were 1:1 matched, comprising the well-balanced IBR and AFR groups. Locoregional recurrence-free survival (LRRFS), disease-free survival (DFS), distant metastasis-free survival (DMFS), and breast cancer-specific survival (BCSS) were compared between the matched groups. RESULTS: After matching, the median follow-up periods were 68 months and 71 months for the IBR and AFR groups, respectively. No significant differences were observed between the IBR and AFR groups regarding the local recurrence (7.2% vs. 5.1%; P = 0.175), regional recurrence (2.1% vs. 1.5%; P = 0.463), or distant metastasis (3.2% vs. 3.2%; P = 1.000) rates. Moreover, no significant difference was observed between the IBR and AFR groups in the LRRFS (hazard ratio, 0.691; 95% CI, 0.433-1.102; P = 0.118), DFS (hazard ratio, 0.709; 95% CI, 0.468-1.076; P = 0.104), DMFS (hazard ratio, 1.006; 95% CI, 0.491-2.059; P = 0.987), or BCSS (hazard ratio, 0.445; 95% CI, 0.111-1.786; P = 0.659). CONCLUSION: In this propensity score-matched analysis of oncologic outcomes in patients with primary breast cancer who underwent immediate breast reconstruction with nipple-/skin-sparing mastectomy, no significant differences were observed between the IBR and AFR groups.

Clinical Course and Predictors of Subsequent Recurrence and Survival of Patients With Ipsilateral Breast Tumor Recurrence.

PURPOSE: To evaluate the clinical course and long-term outcomes of patients with ipsilateral breast tumor recurrence (IBTR) after breast-conserving surgery (BCS) and identify independent prognostic factors for further recurrence. METHODS: In this retrospective study, we reviewed the records of 327 patients who experienced IBTR after undergoing BCS for breast cancer at Asan Medical Center during 1990-2013. Overall survival (OS) after IBTR and cumulative incidence rates of recurrences after IBTR were calculated. The association of clinicopathological factors with survival and the development of further recurrence after IBTR was determined in multivariate analysis. RESULTS: At a median follow-up of 127.7 months, 97 patients experienced recurrence after IBTR. The 5-year and 10-year cumulative incidence rates of recurrence after IBTR were 32% and 41%, respectively. The 5-year and 10-year OS rates after IBTR were 86.6% and 70.3%, respectively. In multivariate analysis, hormone receptor negativity was associated with decreases in OS after IBTR (hazard ratio [HR] 2.83, 95% confidence interval [CI] 1.18-6.78). Patients with longer disease-free interval (DFI) had decreased risks of second recurrence (HR .99, 95% CI .99-1.00), and second locoregional recurrence (LRR) (HR .98, 95% CI .97-.99). Lymphovascular invasion (LVI) of IBTR was associated with increased recurrence rates (second recurrence-free survival, HR 3.58, 95% CI 2.16-5.94; second LRR free survival, HR 5.21, 95% CI 2.77-9.78; second distant metastasis-free survival, 2.11, 95% CI 1.04-4.30) and lower survival rates (OS after IBTR, HR 4.64, 95% CI 2.23-9.67). CONCLUSIONS: Despite subsequent recurrences during long-term follow-up, the survival rates after IBTR remained high. Patients with hormone receptor-negative tumors, shorter DFI, and tumors that present LVI of IBTR had higher risks for recurrence and poor survival rates after IBTR. The study findings may help in understanding the course and prognosis of IBTR patients and identifying high-risk IBTR to establish management strategies.

Is There a Difference in the Diagnosis and Prognosis of Local Recurrence between Autologous Tissue and Implant-Based Breast Reconstruction?

Introduction: Breast reconstruction has become common after total mastectomy; however, certain types of breast reconstruction may be associated with delayed local recurrence or poor survival. Here, we investigated whether there are differences in the diagnosis and prognosis of local recurrence between autologous reconstruction and implant reconstruction. Materials and Methods: A retrospective analysis was performed on patients undergoing breast cancer surgery with autologous tissue or immediate implant reconstruction in a single center (January 2003-December 2017). Patient data including the period from cancer surgery to local recurrence diagnosis, tumor size at the time of recurrence, and survival time after cancer surgery and recurrence detection were analyzed. Results: There was a significant difference (p = 0.021) in the time from surgery to recurrence between the autologous tissue (1,246 days) and implant (909 days) groups. Recurrence tumor size did not differ (autologous: 1.00 cm2 vs. implant: 0.90 cm2; p = 0.813). Survival time after surgery (p = 0.63) and recurrence detection (p = 0.74) did not statistically significant. Conclusions: Statistical difference in the detection time was observed between autologous tissue and implant group. On the other hand, there is no difference in recurrence tumor size or survival time. A further study is necessary to identify the different detection time of local recurrence.

Clinicopathological characteristics and outcomes of malignant adenomyoepithelioma of the breast: a single institution's experience.

BACKGROUND: Malignant adenomyoepithelioma of the breast is a rare tumor and most of relevant literature consists of individual case reports. This study objective was designed to evaluate clinicopathological features and treatment outcomes of 15 cases of malignant adenomyoepithelioma at a single institute. METHODS: A retrospective medical record review was performed for 15 subjects confirmed with malignant adenomyoepithelioma upon postoperative pathological diagnosis at the Asan Medical Center from January 2008 to June 2018. Data regarding age at diagnosis, preoperative biopsy results, operation methods, the status of hormone receptors and HER2, and clinical outcomes were collected. RESULTS: All cases were female patients diagnosed at median age of 50 years. Preoperative core needle biopsy results showed that 40% of the cases (6 out of 15) were benign which was in discordance with the final malignant pathology report. Thirteen cases underwent wide excision with or without sentinel lymph node biopsy (SLNB) and 2 cases had total mastectomy with SLNB. Five of 11 cases (45.5%) were triple negative. Ten of 15 cases underwent postoperative radiation therapy, 3 cases underwent chemotherapy, and 5 cases underwent endocrine therapy. During median follow-up of 55 months, the 5-year overall survival rate was 87.5% and the 5-year disease free survival rate was 91.7%. Two lung metastases developed. One case showed local recurrence 3 years after surgery and radiotherapy and subsequently developed lung metastasis 1 year late. Another case developed lung metastasis one and a half years after surgery in combination with endocrine therapy and neoadjuvant chemotherapy. CONCLUSION: Preoperative core needle biopsy showed inaccurate results for diagnosing malignant adenomyoepithelioma. Malignant adenomyoepithelioma has a high rate of triple negative subtype but has a relatively good prognosis although there is a risk of local and systemic recurrence.

Oncologic Outcomes of Nipple-sparing Mastectomy and Immediate Reconstruction After Neoadjuvant Chemotherapy for Breast Cancer.

OBJECTIVES: To evaluate the oncologic outcomes and risk factors for locoregional recurrence (LRR) and nipple-areola complex recurrence (NR) in a large series of breast cancer patients who underwent nipple-sparing mastectomy (NSM) and immediate reconstruction after neoadjuvant chemotherapy (NACT). SUMMARY OF BACKGROUND DATA: The use of NSM and immediate reconstruction in breast cancer patients receiving NACT is increasing. However, the oncologic safety of this approach is unclear. PATIENTS AND METHODS: A total of 310 breast cancer patients (319 breasts) who underwent NACT and NSM between February 2010 and November 2016 were retrospectively analyzed. Clinical and pathologic factors associated with increased risks of LRR and NR were analyzed using univariate (Chi-square or Fisher exact test) and multivariate (Cox proportional hazard regression model) analyses. RESULTS: During a mean follow-up of 63 ± 22 months, 38 cases had LRR as the first event, including 6 cases of NR as the first event. The 5-year cumulative LRR and NR rates were 11.0% and 1.9%, respectively. In univariate analysis, clinical T stage, pathologic nodal status, histologic grade, lymphovascular invasion, and post-NACT Ki67 status were associated with increased LRR risk, and post-NACT Ki67 status was the only significant risk factor for NR. In multivariate analysis, post-NACT Ki67 ≥10% (hazard ratio, 4.245; 95% confidence interval, 1.865-9.663; P = 0.001) was an independent risk factor for LRR. CONCLUSIONS: NSM and immediate reconstruction seem to be oncologically safe with acceptable LRR and NR rates for appropriately selected breast cancer patients treated with NACT. Post-NACT Ki67 ≥10% was associated with increased risk of LRR or NR, and therefore, necessitates cautious follow-up.