Long-term oncologic outcomes of unselected triple-negative breast cancer patients according to BRCA1/2 mutations.

Triple-negative breast cancer (TNBC) patients are more likely to have BRCA1/2 mutations, with a prevalence rate of about 10-20%. Although several studies have analyzed the oncologic outcomes between BRCA1/2 carriers and non-carriers, the impact on breast cancer patients is still unclear. A retrospective review was performed to determine the long-term outcomes of TNBC patients, focusing on the impact of BRCA1/2 mutations. A total of 953 TNBC patients who underwent primary breast cancer surgery from June 2008 to January 2016 were included. We examined long-term outcomes, including contralateral breast cancer (CBC) incidence, recurrence patterns, and survival rates over a median follow-up of 80.9 months (range 3-152 months). 122 patients (12.8%) had BRCA1/2 mutations. BRCA1/2 mutation carriers were significantly younger at diagnosis and more likely to have a family history of breast/ovarian cancer. CBC incidence at 60, 120, and 150 months was significantly higher in BRCA1/2 mutation carriers compared to non-carriers (P = 0.0250, 0.0063, and 0.0184, respectively). However, there were no significant differences in disease-free survival, overall survival, breast cancer-specific survival, or distant-metastasis-free survival between the two groups. BRCA1/2 mutation status was a significant risk factor for CBC (HR = 6.242, P < 0.0001). Interestingly, among 29 patients with CBC recurrence, 24 patients (82.8%) had recurring TNBC subtype and among the CBC recurrence patients, 19 patients (65.5%) resumed chemotherapy. In the TNBC subtype, appropriate genetic testing and counseling are pivotal for surgical decisions like risk-reducing mastectomy (RRM). Furthermore, long-term surveillance is warranted, especially in BRCA1/2 carriers who did not receive RRM.

Impact of residual microcalcifcations on prognosis after neoadjuvant chemotherapy in breast cancer patients.

BACKGROUND: Residual microcalcifications after neoadjuvant chemotherapy (NAC) are challenging for deciding extent of surgery and questionable for impact on prognosis. We investigated changes in the extent and patterns of microcalcifications before and after NAC and correlated them with pathologic response. We also compared prognosis of patients depending on presence of residual microcalcifications after NAC. METHODS: A total of 323 patients with invasive breast carcinoma treated with neoadjuvant chemotherapy at Kangbuk Samsung Hospital and Samsung Medical center from March 2015 to September 2018 were included. Patients were divided into four groups according to pathologic response and residual microcalcifications. Non-pCRw/mic group was defined as breast non-pCR with residual microcalcifications. Non-pCRw/o mic group was breast non-pCR without residual microcalcifications. pCRw/mic group was breast pCR with residual microcalcifications. pCRw/o mic group was breast pCR without residual microcalcifications. The first aim of this study is to investigate changes in the extent and patterns of microcalcifications before and after NAC and to correlate them with pathologic response. The second aim is to evaluate oncologic outcomes of residual microcalcifications according to pathologic response after NAC. RESULTS: There were no statistical differences in the extent, morphology, and distribution of microcalcifications according to pathologic response and subtype after NAC (all p > 0.05). With a median follow-up time of 71 months, compared to pCRw/o mic group, the hazard ratios (95% confidence intervals) for regional recurrence were 5.190 (1.160-23.190) in non-pCRw/mic group and 5.970 (1.840-19.380) in non-pCRw/o mic group. Compared to pCRw/o mic group, the hazard ratios (95% CI) for distant metastasis were 8.520 (2.130-34.090) in non-pCRw/mic group, 9.120 (2.850-29.200) in non-pCRw/o mic group. Compared to pCRw/o mic, the hazard ratio (95% CI) for distant metastasis in pCRw/mic group was 2.240 (0.230-21.500) without statistical significance (p = 0.486). CONCLUSIONS: Regardless of residual microcalcifications, patients who achieved pCR showed favorable long term outcome compared to non-pCR group.

Outcomes of whole breast radiation therapy in Asian breast cancer patients with prior cosmetic implants.

BACKGROUND: As breast augmentation has become more popular, an increasing number of women with augmented breasts require treatment for breast cancer. This study aimed to assess the outcomes of postoperative whole breast radiation therapy (WB-RT) in Asian patients with breast cancer who underwent prior cosmetic breast implantation. METHODS: We retrospectively reviewed the medical records of 61 patients with breast cancer who had prior cosmetic breast implants (prior-CBI) and underwent breast-conserving surgery (BCS) and WB-RT between 2015 and 2020. The median implant volume was 238.8 cc, with a median interval of 84.7 months between the prior-CBI and BCS. WB-RT was administered with either conventional fractionation (CF-RT) at 50 Gy in 25 fractions (N = 36) or hypofractionation (HF-RT) at 42.6 Gy in 16 fractions (N = 25). The incidences of implant-related complications (IRC) and their contributing factors were analyzed. RESULTS: After a median follow-up of 43.5 months, the 3-year cumulative incidences of IRC and implant loss were 17.2% and 4.9%, respectively. Among the four (6.6%) patients who opted for implant removal after RT, three were potentially related to RT-related capsular contracture. There was no difference in the 3-year cumulative IRC rates following CF-RT and HF-RT (12.2% and 26.7%, respectively; p = 0.120). The risk factors for IRC included a larger implant size (> 260 cc) and a higher ratio of breast tissue to implant volume. CONCLUSIONS: This study demonstrated a favorable safety profile of WB-RT for treatment of breast cancer in Asian women with prior-CBI. The integration of HF-RT following BCS was thought to be a feasible approach.

Oncologic Outcomes of Immediate Breast Reconstruction in the Setting of Neoadjuvant Chemotherapy: A Long-term Follow-up Study of a Matched Cohort.

PURPOSE: Despite the increasing use of immediate breast reconstruction (IBR), its oncologic safety in the setting of neoadjuvant chemotherapy (NACT) needs to be comprehensively clarified in breast cancer management. The objective of the present study was to analyze the oncologic safety of IBR following NACT. METHODS: In total, 587 patients with breast cancer who underwent a total mastectomy (TM) with IBR after NACT between 2008 and 2017 at a single institution were retrospectively reviewed. The reviewed patients with IBR following skin-sparing mastectomy (SSM) or nipple-sparing mastectomy (NSM) were matched 1:3 to patients who underwent TM alone after NACT. Matching variables included age, clinical T and N stages before NACT, response to NACT, pathologic T and N stages, and molecular subtypes. RESULTS: After propensity score matching, 95 patients who underwent IBR following SSM/NSM after NACT (IBR group) and 228 patients who underwent TM alone after NACT (TM group) were selected. The median follow-up period was 73 (range, 5-181) months after matching. After matching, there were no significant differences between the two groups in 5-year locoregional recurrence-free survival (88.8% vs. 91.2%, p = 0.516), disease-free survival (67.3% vs. 76.6%, p = 0.099), distant metastasis-free survival (71.9% vs. 81.9%, p = 0.057), or overall survival (84.1% vs. 91.5, p = 0.061) rates. In multivariate analyses, conducting IBR was not associated with increased risks for locoregional recurrence, any recurrence, distant metastasis, or overall death. CONCLUSION: Our findings suggest that IBR following SSM/NSM elicits comparable long-term oncologic outcomes to those of TM alone in the setting of NACT.

The Impact of HER2-Low Expression on Oncologic Outcomes in Hormone Receptor-Positive Breast Cancer.

Breast cancer is a prevalent malignancy with increasing incidence, particularly in Asian countries. Classification based on estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status is pivotal in determining treatment. Recent advances have challenged the traditional dichotomy in HER2 classification, prompting investigation into the HER2-low subtype's characteristics and outcomes. This retrospective study analyzed 10,186 non-metastatic hormone receptor (HR)-positive, HER2-negative breast cancer cases treated from 2008 to 2020. Data encompassed clinical, pathological, and treatment information. Oncologic outcomes included disease-free survival (DFS), overall survival (OS), and breast cancer-specific survival (BCSS). In total, 56.5% were HER2-low cases. Differences in patient characteristics were noted, with more BRCA1/2 mutations and higher mastectomy rates in the HER2-low group (p = 0.002, p < 0.001, respectively). Fewer received adjuvant chemotherapy or radiation therapy, and fewer histologic and nuclear grade 1 tumors were identified (all p < 0.001). With a median follow-up of 64 months (range: 13-174), HER2-low cases exhibited better DFS, OS, and BCSS than HER2-0 cases (p = 0.012, p = 0.013, and p = 0.013, respectively). Notably, the prognosis differed between premenopausal and postmenopausal subgroups, with BCSS benefitting premenopausal patients (p = 0.047) and DFS and OS benefitting postmenopausal patients in the HER2-low group (p = 0.004, p = 0.009, respectively). Multivariate analysis confirmed HER2 status as an independent predictor of these outcomes (p = 0.010, p = 0.008, and p = 0.014, respectively). This extensive single-center study elucidates the favorable prognosis associated with HER2-low status in HR-positive breast cancer. However, this effect differs among premenopausal and postmenopausal patients, necessitating further research into the underlying tumor biology.

The Role of Post-Mastectomy Radiotherapy in T1-2N1 Breast Cancer Patients: Propensity Score Matched Analysis.

This study aimed to evaluate the role of post-mastectomy radiotherapy (PMRT) in T1-2N1 breast cancer. Between 2006 and 2014, a total of 504 patients with T1-2N1 breast cancer were analyzed. PMRT was administered to 71 patients, and 1:2 propensity score matching (PSM) was performed between the PMRT and non-PMRT groups. Loco-regional control (LRC), disease-free survival (DFS), and overall survival (OS) rates were compared according to PMRT status. Thirteen and one loco-regional recurrences were observed in the PMRT and non-PMRT groups, respectively. Before PSM, the 8-year LRC, DFS, and OS rates in the non-PMRT and PMRT groups were 98.5% and 96.5% (p = 0.426), 89.7% and 91.2% (p = 0.700), and 91.5% and 92.1% (p = 0.679), respectively. Corresponding rates were 95.6% and 96.5% (p = 0.365), 84.1% and 91.2% (p = 0.185), and 88.4% and 92.1% (p = 0.276), respectively, after PSM. Multivariate analysis showed that three lymph node metastases were prognostic for LRC and DFS rates and LVI for OS rate. Arm lymphedema developed in 32.4% of patients who received PMRT, which was significantly higher than the non-PMRT group (p < 0.001). Contributions of PMRT for improvement of treatments outcomes in T1-2N1 breast cancer patients were not evident, while the incidence of arm lymphedema significantly increased after PMRT. Further prospective trials are required to re-evaluate the role of PMRT.

Benefit of postoperative regional nodal irradiation in patients receiving preoperative systemic therapy with docetaxel/carboplatin/trastuzumab/pertuzumab for HER2-positive breast cancer.

AIM: The role of regional nodal irradiation (RNI) after preoperative systemic treatment (PST) with targeted therapy for HER2-positive breast cancer remains uncertain. This study aimed to investigate the impact of RNI on locoregional recurrence (LRR) and disease-free survival (DFS) outcomes after docetaxel/carboplatin/trastuzumab/pertuzumab (TCHP) for PST. METHODS: We retrospectively analyzed 255 patients who were treated with six cycles of TCHP between 2016 and 2019. The patients were divided into four groups based on clinical nodal involvement: group A, with no nodal disease; group B, with axillary lymph node (AXL) level I; group C, with AXL level I with II/III; and group D, with supraclavicular or internal mammary nodes. RESULTS: The RNI group had more advanced nodal disease (C/D) than the no RNI group (56.9 % vs. 6.8 %). With a median follow-up of 51.3 months, there were two (0.8 %), three (1.2 %), and 15 (5.9 %) local, regional, and distant metastases, respectively. LRR did not differ significantly according to the RNI (2.6 % vs. 1.0 %, p = 0.651). Group D had the most frequent distant metastases (17.5 %; p = 0.005). The 4-year DFS rate was 92.7 %, and DFS did not improve significantly after RNI (p = 0.074). When stratified by clinical nodal groups and pathological axillary response, RNI had no effect on LRR/DFS outcomes. CONCLUSION: With a rare incidence of LRR, RNI did not significantly affect LRR or DFS in patients with HER2-positive breast cancer after with PST-TCHP. However, intensive systemic treatment is required for advanced diseases (C/D). Selective de-intensified RNI and intensified systemic treatment should be investigated in future studies.

Incidence of and Influencing Factors for Arm Lymphedema After Salvage Treatment for an Isolated Locoregional Recurrence of Breast Cancer.

PURPOSE: Data on subsequent arm lymphedema (SAL) after salvage treatment for locoregional recurrence (LRR) of breast cancer are limited. We conducted a study to evaluate the risk of SAL in patients with LRR. METHODS: We reviewed the data of patients with breast cancer who had LRR and were initially diagnosed between January 2003 and December 2017. Among the 214 patients who received curative salvage treatment, most had local (n = 125, 57.9%), followed by regional (n = 73, 34.1%), and locoregional (n = 16, 7.9%) recurrences. A competing risk analysis considering the factors of death and a second LRR were performed to exclude potential malignant lymphedema. We used the Fine-Gray subdistribution hazards model to estimate the hazard ratio (HR) for comparing the risk of SAL. RESULTS: With a median follow-up duration of 41.4 months (interquartile range, 25.6-65.1), 51 patients (23.8%) experienced SAL with a median interval of 9.9 months after treatment. The two-year cumulative incidence of SAL was 12.7%. Among the 18 patients with initial lymphedema, nine (50.0%) developed SAL. Multivariate analysis revealed that a history of lymphedema (HR, 4.61; p < 0.001) and taxane-based salvage chemotherapy (HR, 2.38; p = 0.009) were significantly associated with SAL development. CONCLUSION: Salvage treatment for LRR-induced SAL was performed in 24% of the patients. A history of initial lymphedema and salvage taxane-based chemotherapy increases the risk of developing SAL. Therefore, close surveillance for the incidence of SAL is required in patients opting for salvage treatment for LRR.

Risk factors of breast cancer recurrence in pathologic complete response achieved by patients following neoadjuvant chemotherapy: a single-center retrospective study.

Objective: Pathologic complete response (pCR) of breast cancer after neoadjuvant chemotherapy (NAC) is highly related to molecular subtypes. Patients who achieved tumor pCR after NAC have a better prognosis. However, despite of better prognosis, pCR patients have a potential for recurrence. There is little evidence of risk factors of recurrence in patients with pCR. We aim to analyze factors associated with tumor recurrence in patients who achieved pCR. Methods: This study retrospectively reviewed the data of patients diagnosed with breast cancer who achieved pCR after receiving NAC between January 2009 and December 2018 in Samsung Medical Center. pCR was defined as no residual invasive cancer in the breast and axillary nodes even if there is residual ductal carcinoma in situ (ypT0 or ypTis with ypN0). Breast cancers are classified into 4 subtypes based on hormone receptors (HR) and human epithelial growth factor receptor 2 (HER2) status. Patients who had bilateral breast cancer, ipsilateral supraclavicular or internal mammary lymph node metastasis, inflammatory breast cancer, distant metastasis, unknown subtype, and histologically unique case were excluded from the study. Results: In total 483 patients were included in this study except for patients who corresponded to the exclusion criteria. The median follow-up duration was 59.0 months (range, 0.5-153.3 months). Breast cancer recurred in 4.1% of patients (20 of 483). There was a significant difference in clinical T (P = 0.004) and clinical N (P = 0.034) stage in the Kaplan-Meier curve for disease-free survival. Molecular subtypes (P = 0.573), Ki67 (P = 1.000), and breast surgery type (P = 0.574) were not associated with tumor recurrence in patients who achieved pCR after NAC. In the clinical T stage and clinical N stage, there was a significant difference between recurrence and no-recurrence groups (clinical T stage; P = 0.045, clinical N stage; P = 0.002). Univariable Cox regression revealed statistical significance in the clinical T stage (P = 0.049) and clinical N stage (P = 0.010), while multivariable Cox regression demonstrated non-significance in the clinical T stage (P = 0.320) and clinical N stage (P = 0.073). Conclusion: Results in this study showed that clinical T, clinical N stage, and molecular subtypes were not statistically significant predictors of recurrence in patients who achieved pCR after NAC. In spite of that, pCR after NAC may be more important than clinical staging and molecular subtype in early breast cancer. In addition, escalated treatments for patients with HER2 + or triple-negative tumors would be considered with a strict patient selection strategy to prevent over-treatment as well as achieve pCR.

Oncologic efficacy of gonadotropin-releasing hormone agonist in hormone receptor-positive very young breast cancer patients treated with neoadjuvant chemotherapy.

BACKGROUND: Breast cancer in young women has been shown to have an aggressive behavior and poor prognosis. AIM: To evaluate the outcomes of young hormone receptor (HR)-positive patients with breast cancer treated with neoadjuvant chemotherapy (NAC), and the oncologic efficacy of gonadotropin-releasing hormone (GnRH) agonists. METHODS: This retrospective study involved a prospectively enrolled cohort. We included patients diagnosed with invasive breast cancer who were treated with NAC followed by curative surgery at the Samsung Medical Center and Samsung Changwon Hospital between January 2006 and December 2017. Among patients with HR-positive and human epidermal grow factor 2 (HER2)-negative breast cancer, we analyzed the characteristics and oncology outcomes between the patients equal to or younger than 35 years and the patients older than 35 years. RESULTS: Among 431 patients with NAC and HR-positive/HER2-negative breast cancer, 78 were 35 years old or younger, and 353 patients were older than 35 years. The median follow-up was 71.0 months. There was no statistically significant difference in disease free survival (DFS, P = 0.565) and overall survival (P = 0.820) between the patients equal to or younger than 35 years and the patients older than 35 years. The two groups differed in that the GnRH agonist was used more frequently in the group of patients equal to or younger than 35 years than in the other group (52.4% vs 11.2%, P < 0.001). Interestingly, for the DFS according to the GnRH agonist in the group of patients equal to or younger than 35 years, patients treated with the GnRH agonist had better DFS (P = 0.037). CONCLUSION: Administration of GnRH agonists might improve the DFS rate of HR-positive/HER2-negative breast cancer in the equal to or younger than 35 years group of patients with NAC.

Genomic characteristics of triple negative apocrine carcinoma: a comparison to triple negative breast cancer.

Apocrine carcinoma is a rare breast cancer subtype. As such, the genomic characteristics of apocrine carcinoma with triple negative immunohistochemical results (TNAC), which has been treated as triple negative breast cancer (TNBC), have not been revealed. In this study, we evaluated the genomic characteristics of TNAC compared to TNBC with low Ki-67 (LK-TNBC). In the genetic analysis of 73 TNACs and 32 LK-TNBCs, the most frequently mutated driver gene in TNAC was TP53 (16/56, 28.6%), followed by PIK3CA (9/56, 16.1%), ZNF717 (8/56, 14.3%), and PIK3R1 (6/56, 10.71%). Mutational signature analysis showed enrichment of defective DNA mismatch repair (MMR)-related signatures (SBS6 and SBS21) and the SBS5 signature in TNAC, whereas an APOBEC activity-associated mutational signature (SBS13) was more prominent in LK-TNBC (Student's t test, p < 0.05). In intrinsic subtyping, 38.4% of TNACs were classified as luminal A, 27.4% as luminal B, 26.0% as HER2-enriched (HER2-E), 2.7% as basal, and 5.5% as normal-like. The basal subtype was the most dominant subtype (43.8%) in LK-TNBC (p < 0.001), followed by luminal B (21.9%), HER2-E (21.9%), and luminal A (12.5%). In the survival analysis, TNAC had a five-year disease-free survival (DFS) rate of 92.2% compared to 59.1% for LK-TNBC (P = 0.001) and a five-year overall survival (OS) rate of 95.3% compared to 74.6% for LK-TNBC (P = 0.0099). TNAC has different genetic characteristics and better survival outcomes than LK-TNBC. In particular, normal-like and luminal A subtypes in TNAC have much better DFS and OS than other intrinsic subtypes. Our findings are expected to impact medical practice for patients diagnosed with TNAC.

Progesterone Receptor Expression Level Predicts Prognosis of Estrogen Receptor-Positive/HER2-Negative Young Breast Cancer: A Single-Center Prospective Cohort Study.

BACKGROUND: Although estrogen receptor (ER) expression levels affect the prognosis of breast cancer, studies about progesterone receptor (PR) expression levels are insufficient, especially in young breast cancer (YBC). The purpose of this study was to compare clinical characteristics and prognosis according to PR expression levels in invasive breast cancer patients. METHODS: A prospective cohort study was conducted to identify YBC patients with invasive carcinoma diagnosed at an age of less than 40 years old between 2013 and 2018. Clinicopathologic features and prognosis of ER-positive and human epidermal growth factor receptor 2 (HER2)-negative patients were investigated. Patients were stratified into strong PR (PR-positive cell proportion > 10%), low PR (PR-positive cell proportion = 1~10%), and PR-negative (PR-positive cell proportion < 1%). RESULTS: Among 458 patients enrolled, 386 (84.3%), 26 (5.7%), and 46 (10.0%) were categorized into strong PR, low PR, and PR-negative groups, respectively. The median follow-up duration was 58.6 months. Compared with the strong PR group, low PR and PR-negative groups were more likely to have high Ki-67 and a high nuclear grade. Low R and PR-negative groups had significantly worse disease-free survival (DFS) and distant metastasis-free survival (DMFS) than the strong PR group (p = 0.0033, p = 0007). Low PR group had an even higher risk of distant metastasis than PR-negative patients. Low PR patients and PR-negative had significantly lower overall survival (OS) rates than strong PR. CONCLUSION: Low PR might be a prognostic factor of ER-positive/HER2-negative in YBC.

Trends of axillary surgery in breast cancer patients with axillary lymph node metastasis: a comprehensive single-center retrospective study.

Purpose: Based on the results of previous trials, de-escalation of axillary surgery after neoadjuvant chemotherapy (NAC) has increased in patients with axillary lymph node (ALN) metastasis at presentation. This study aimed to review the trends of axillary surgery by time period and molecular subtype in patients with ALN metastasis. Methods: We analyzed the rates of sentinel lymph node biopsy (SLNB) and ALN dissection (ALND) based on time period and subtype. The time period was divided into 3 subperiods to determine the rate of axillary surgery type over time (period 1, from 2009 to 2012; period 2, from 2013 to 2016; and period 3, from 2017 to July 2019). Results: From 2009 to July 2019, 2,525 breast cancer patients underwent surgery. Based on subtype, the ALND rate of hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) disease decreased by 13.0% from period 1 to period 3 (period 1, 99.4%; period 2, 97.5%; and period 3, 86.4%; P < 0.001). Conversely, the ALND rate in HR+/HER2+, HR-/HER2+, and triple-negative breast cancer (TNBC) significantly decreased by 43.7%, 48.8%, and 35.2% in period 1, period 2, and period 3, respectively (P < 0.001). In the patient group receiving NAC, HR+/HER2- had a significantly higher ALND rate (84.1%) than HR+/HER2+, HR-/HER2+, and TNBC (60.8%, 62.3%, and 70.7%, respectively; P < 0.001). Conclusion: The SLNB rate in patients with ALN metastasis has increased over time. However, the ALND rate in HR+/HER2- was significantly higher than in other subtypes.

Prediction Model for Postoperative Quality of Life Among Breast Cancer Survivors Along the Survivorship Trajectory From Pretreatment to 5 Years: Machine Learning-Based Analysis.

BACKGROUND: Breast cancer is the most common cancer and the most common cause of cancer death in women. Although survival rates have improved, unmet psychosocial needs remain challenging because the quality of life (QoL) and QoL-related factors change over time. In addition, traditional statistical models have limitations in identifying factors associated with QoL over time, particularly concerning the physical, psychological, economic, spiritual, and social dimensions. OBJECTIVE: This study aimed to identify patient-centered factors associated with QoL among patients with breast cancer using a machine learning (ML) algorithm to analyze data collected along different survivorship trajectories. METHODS: The study used 2 data sets. The first data set was the cross-sectional survey data from the Breast Cancer Information Grand Round for Survivorship (BIG-S) study, which recruited consecutive breast cancer survivors who visited the outpatient breast cancer clinic at the Samsung Medical Center in Seoul, Korea, between 2018 and 2019. The second data set was the longitudinal cohort data from the Beauty Education for Distressed Breast Cancer (BEST) cohort study, which was conducted at 2 university-based cancer hospitals in Seoul, Korea, between 2011 and 2016. QoL was measured using European Organization for Research and Treatment of Cancer QoL Questionnaire Core 30 questionnaire. Feature importance was interpreted using Shapley Additive Explanations (SHAP). The final model was selected based on the highest mean area under the receiver operating characteristic curve (AUC). The analyses were performed using the Python 3.7 programming environment (Python Software Foundation). RESULTS: The study included 6265 breast cancer survivors in the training data set and 432 patients in the validation set. The mean age was 50.6 (SD 8.66) years and 46.8% (n=2004) had stage 1 cancer. In the training data set, 48.3% (n=3026) of survivors had poor QoL. The study developed ML models for QoL prediction based on 6 algorithms. Performance was good for all survival trajectories: overall (AUC 0.823), baseline (AUC 0.835), within 1 year (AUC 0.860), between 2 and 3 years (AUC 0.808), between 3 and 4 years (AUC 0.820), and between 4 and 5 years (AUC 0.826). Emotional and physical functions were the most important features before surgery and within 1 year after surgery, respectively. Fatigue was the most important feature between 1 and 4 years. Despite the survival period, hopefulness was the most influential feature on QoL. External validation of the models showed good performance with AUCs between 0.770 and 0.862. CONCLUSIONS: The study identified important factors associated with QoL among breast cancer survivors across different survival trajectories. Understanding the changing trends of these factors could help to intervene more precisely and timely, and potentially prevent or alleviate QoL-related issues for patients. The good performance of our ML models in both training and external validation sets suggests the potential use of this approach in identifying patient-centered factors and improving survivorship care.

Impact of Adjuvant Hormone Therapy on Sleep, Physical Activity, and Quality of Life in Premenopausal Breast Cancer: 12-Month Observational Study.

PURPOSE: This study aimed to investigate the differences in sleep disturbance changes between patients receiving two hormone therapies ("tamoxifen plus ovarian function suppression group [T+OFS group]" versus "tamoxifen group [T group]") and the chronological changes in sleep disturbances in each group. METHODS: Premenopausal women with unilateral breast cancer who underwent surgery and were scheduled to receive hormone therapy (HT) with tamoxifen alone or with tamoxifen plus gonadotropin-releasing hormone (GnRH) agonist for ovarian function suppression were included. The enrolled patients wore an actigraphy watch for two weeks and completed questionnaires (insomnia, sleep quality, physical activity [PA], and quality of life [QOL]) at five time points: immediately before HT and 2, 5, 8, and 11 months after HT. RESULTS: Among the 39 enrolled patients (21 and 18 patients in the T+OFS group and T group, respectively), 25 (17 and 8 patients in the T+OFS group and T group, respectively) were finally analyzed. There were no differences between the two groups in time-dependent changes in insomnia, sleep quality, total sleep time, rapid eye movement sleep rate, QOL, and PA; however, the severity of hot flashes was significantly higher in the T+OFS group than in the T group. Although the interaction between group and time was not significant, insomnia and sleep quality significantly worsened at 2-5 months of HT when changes over time were analyzed within the T+OFS group. In both the groups, PA and QOL were maintained without significant changes. CONCLUSION: Unlike tamoxifen alone, tamoxifen plus GnRH agonist initially worsened insomnia and sleep quality, but gradually improved with long-term follow-up. Patients who initially experience insomnia during tamoxifen plus GnRH agonist administration can be reassured based on the results of this study, and active supportive care may be used during this period. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04116827.

The efficacy and safety of an indocyanine green-hyaluronic acid mixture (LuminoMark™) for localization in patients with non-palpable breast lesions: A multicenter, randomized, open-label, parallel phase 3 clinical trial.

Purpose: The incidence of early tumor detection is increasing due to popularization of breast cancer screening and the development of imaging techniques. Thus, suitable preoperative localization is required for proper diagnosis and treatment of non-palpable breast lesions. The purpose of this study was to evaluate the efficacy and safety of indocyanine green (ICG)-hyaluronic acid (HA) mixture for lesion localization compared to activated charcoal. Methods: This was a multicenter, randomized, open-label, parallel phase 3 clinical trial performed at four centers in Korea. Female patients scheduled for surgery to remove non-palpable breast lesions were enrolled. One hundred and nine patients were randomly assigned to a control group (activated charcoal: 0.3. - 1 mL) or a study group (ICG-HA mixture, 0.2 mL) for the localization of a breast lesion. The primary endpoint was the accuracy of resection. Secondary endpoints included the technical success rate, histopathological accuracy, skin pigmentation rate, and adverse event rate. Results: A total of 104 patients were eligible for per-protocol analysis (control group, n = 51; study group, n = 53). The accuracy of resection in the study group was not inferior to that of the control group (90.57% vs. 98.04%, 95% confidence interval (CI): -2.31 - 18.91, p = 0.21). There was no statistically significant difference in technical success rate between the two groups (marking on breast skin: p = 0.11, marking on the excised specimen: p = 0.12). However, there were statistically significant differences in histopathological accuracy (0.26 ± 0.13 vs. 0.33 ± 0.17, p = 0.01) and skin pigmentation rate (0.00% vs. 30.77%, p< 0.01). Adverse events were not reported in either group. Conclusions: When localization was performed using ICG-HA, the accuracy of resection was not inferior to that of activated charcoal. However, skin pigmentation rate was significantly lower. In conclusion, ICG-HA is effective and safe for localizing of non-palpable breast lesions.

Clinical Characteristics and Prognosis of Metaplastic Breast Cancer Compared with Invasive Ductal Carcinoma: A Propensity-Matched Analysis.

BACKGROUND: Metaplastic breast cancer (MpBC) is an aggressive histologic type of breast cancer. Although MpBC has a poor prognosis and is responsible for a large proportion of breast cancer mortalities, the clinical features of MpBC compared with invasive ductal carcinoma (IDC) are not well known, and the optimal treatment has not been identified. METHODS: We retrospectively reviewed medical records of 155 MpBC patients and 16,251 IDC cases who underwent breast cancer surgery in a single institution between January 1994 and December 2019. The two groups were matched 1:4 by age, tumor size, nodal status, hormonal receptor status, and HER2 status using propensity-score matching (PSM). Finally, 120 MpBC patients were matched with 478 IDC patients. Disease-free survival and overall survival of MpBC and IDC patients both before and after PSM were analyzed by Kaplan-Meier survival, and multivariable Cox regression analysis was performed to identify variables affecting long-term prognosis. RESULTS: The most common subtype of MpBC was triple-negative breast cancer, and nuclear and histologic grades were higher than those of IDC. Pathologic nodal staging of the metaplastic group was significantly lower than that of the ductal group, and more frequent adjuvant chemotherapy was performed in the metaplastic group. Multivariable Cox regression analysis indicated that MpBC was an independent prognostic factor for disease-free survival (HR = 2.240; 95% CI, 1.476-3.399, p = 0.0002) and overall survival (HR = 1.969; 95% CI, 1.147-3.382, p = 0.0140). However, survival analysis revealed no significant difference between MpBC and IDC patients in disease-free survival (HR = 1.465; 95% CI, 0.882-2.432, p = 0.1398) or overall survival (hazard ratio (HR) = 1.542; 95% confidential interval (CI), 0.875-2.718, p = 0.1340) after PSM. CONCLUSION: Although the MpBC histologic type had poor prognostic factors compared with IDC, it can be treated according to the same principles as aggressive IDC.

Feasibility and usability of a personalized mHealth app for self-management in the first year following breast cancer surgery.

This study investigated the feasibility and usability of a personalized mobile health (mHealth) app for self-management during the year following breast cancer surgery. Twenty-nine participants were instructed to use an app and smart band immediately after discharge. Only 18 completed the study. Their perceived necessity and satisfaction for main domains and app were assessed at 1, 2, 4, 6, 9, and 12 months. A self-reporting questionnaire assessed usability at 12 months. Consequently, retention rate as measures of feasibility showed a mean of 75.8%. Exercise and diet management were the most accessed app domains. Perceived necessity was higher than satisfaction. The mean usability score was 80.2. Most participants found the app useful and effective as a delivery for healthcare. Further, 94% of them were willing to pay for and recommend it. Thus, mHealth app can help breast cancer patients improve their healthy behaviors and healthcare further. This study provides insights for designing long-term randomized controlled trials using mHealth interventions.

Predicting the Response of Neoadjuvant Chemotherapy in Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer With Axillary Lymph Node Metastasis by Multigene Assay.

PURPOSE: The GenesWell™ breast cancer test (BCT) is a recently developed multigene assay that predicts the risk of distant recurrence in patients with hormone receptor-positive (HR+) and human epidermal growth factor-2 negative (HER2-) early breast cancer (BC). The ability of this assay to predict the response to neoadjuvant chemotherapy (NACT) has not been established to date. METHODS: Biopsy specimens from HR+/HER2- BC patients with axillary lymph node (LN) metastasis who underwent NACT were analyzed using the BCT score. The modified BCT score was developed and patients classified into high-and low-response groups. A total of 88 patients were available for the BCT score among the 108 eligible patients. The median follow-up duration was 35.9 (7.8-128.5) months. RESULTS: Among them, 61 (65.1%) had cN1 and 53 (60.2%) had cT1 or cT2 disease. The BCT score was low in 25 (28.4%) patients and high in 63 (71.6%). Among the 50 patients with pathologic complete response or partial response, 41 (82.0%) were in the high BCT score group and 9 (18.0%) were in the low BCT score group. Among the 38 patients with stable or progressive disease, 22 (57.9%) were in the high BCT score group and 16 (42.1%) were in the low BCT score group (p = 0.025). Ki-67 before NACT was a significant factor for predicting tumor response (p = 0.006; 3.81 [1.50-10.16]). The BCT score showed a significant response to NACT (p = 0.016; 4.18 [1.34-14.28]). Distant metastasis-free survival was significantly different between the high- and low-response groups (p = 0.004). CONCLUSION: We demonstrated that the BCT score predicts NACT responsiveness in HR+/HER2- BC with LN metastasis and might help determine whether NACT should be performed. Further studies are required to validate these results.

Is Pathologic Axillary Staging Valid If Lymph Nodes Are Less than 10 with Axillary Lymph Node Dissection after Neoadjuvant Chemotherapy?

Introduction: The aim of this study was to evaluate the prognostic value of the number of lymph nodes removed in breast cancer patients who undergo axillary lymph node dissection (ALND) after neoadjuvant chemotherapy (NAC). Methods: We included patients who were diagnosed with invasive breast cancer and cytology with proven involved axillary node metastasis at diagnosis and treated with NAC followed by curative surgery at Samsung Medical Center between January 2007 and December 2015. The primary outcomes were disease-free survival (DFS) and overall survival (OS). Results: Among 772 patients with NAC and ALND, there were 285 ypN0, 258 ypN1, 135 ypN2, and 94 ypN3 cases. The median follow-up duration was 69.0 months. The group with less than 10 lymph nodes number (<10 nodes group) included 123 patients and the group with 10 or more lymph nodes number (≥10 nodes group) included 649 patients. There were no significant differences in DFS (p = 0.501) or OS (p = 0.883) between the two groups. In the ypN0 subgroup, the <10 nodes group had worse DFS than ≥10 nodes group (p = 0.024). In the ypN1 subgroup, there were no significant differences in DFS (p = 0.846) or OS (p = 0.774) between the two groups. In the ypN2 subgroup, the <10 nodes group had worse DFS (p = 0.025) and OS (p = 0.031) than ≥10 nodes group Conclusion: In ypN0 and ypN2 subgroups, breast cancer patients with less than 10 lymph nodes number in ALND after NAC might be considered for additional staging or closer surveillance when compared to patients with 10 or more than lymph node.