Adverse effects of tamoxifen treatment on bone mineral density in premenopausal patients with breast cancer: a systematic review and meta-analysis.

BACKGROUND: It is well known that adjuvant tamoxifen treatment for breast cancer in postmenopausal women decreased bone loss. However, the effects of adjuvant tamoxifen therapy on bone mineral density (BMD) in premenopausal patients with breast cancer remains uncertain. Tamoxifen would have a potential impact of premenopausal BMD on health. The aim of this meta-analysis was to assess this in premenopausal women with primary breast cancer. METHODS: Through April 2020, studies reporting BMD changes of lumbar spine or hip in premenopausal women with primary breast cancer treated with adjuvant tamoxifen and tamoxifen plus chemotherapy or ovarian function suppression (OFS) were collected from EMBASE and PubMed. The meta-analysis was performed using random effects model of the standardized mean difference (SMD) of BMD in patients. RESULTS: A total of 1432 premenopausal patients were enrolled in eight studies, involving 198 patients treated with tamoxifen alone in three studies. After a 3-year median follow-up, adjuvant tamoxifen decreased the lumbar spinal and hip BMD by as much as an SMD of -1.17 [95% confidence interval (CI); -1.58 to -0.76)] and -0.66 (95% CI, -1.55 to 0.23), respectively. In subgroup analysis in patients treated adjuvant tamoxifen and tamoxifen plus chemotherapy or OFS according to follow-up duration, the bone change of < 3 years follow-up group was -0.03 SMD (95% CI, -0.47 to 0.41) and that of ≥ 3 years follow-up group was -1.06 SMD (95% CI, -1.48 to -0.64). Compared with patients who received tamoxifen alone, patients who received combination therapy with chemotherapy or OFS showed lesser bone loss at the lumbar spine. CONCLUSIONS: Our meta-analysis demonstrated that adjuvant tamoxifen therapy in premenopausal patients caused bone loss after 3 years of follow-up, especially at the lumbar spines. For a definite evaluation of the adverse effects of tamoxifen on bone, it is necessary to accumulate more relevant studies.

Temporal Trend in Uptake of the National General Health Checkups and Cancer Screening Program among Korean Women with Breast Cancer.

PURPOSE: This study assessed the temporal trends of uptake of national general health and cancer screening among women with breast cancer in Korea between 2009 and 2016. MATERIALS AND METHODS: We retrospectively analyzed the claims data from the Korean National Health Insurance Service database. Participants included 101,403 breast cancer patients diagnosed between 2009 and 2016. Information on participation in national screening programs, including breast cancer screening, general health, and gastric, colorectal, and cervical cancers, up to 2020 was collected. Screening participation rates within the first 2 and 5 years postdiagnosis were calculated by diagnosis year and fitted with joinpoint regression models to assess temporal trends. RESULTS: Overall, the participation rate in breast cancer screening within 2 years postdiagnosis increased from 10.9% to 14.0% from 2009-2016, with an annual percentage change (APC) of 3.7% (p < 0.05). The participation rate in breast cancer screening was lower than that in general health checkup and screening for other cancers within 2 and 5 years postdiagnosis. A steady increase in screening trends was also observed for general health, gastric, colorectal, and cervical cancers, with APC of 5.3%, 5.7%, 6.9%, and 7.6% in the 2-year postdiagnosis rate, and APC of 3.6%, 3.7%, 3.7%, and 4.4% in 5-year postdiagnosis rate, respectively. The screening rate was highest among age groups 50-59 and 60-69 in 2009 and significant upward trends were observed in all age groups for general health checkup and gastric, colorectal, and cervical cancer screening. CONCLUSION: Among female breast cancer survivors in Korea, the uptake rate of screenings for general health and various cancers, including breast, gastric, colorectal, and cervical cancers, has shown a gradual increase in recent years.

ASAP1 Expression in Invasive Breast Cancer and Its Prognostic Role.

Breast cancer is a major global health burden with high morbidity and mortality rates. Previous studies have reported that increased expression of ASAP1 is associated with poor prognosis in various types of cancer. This study was conducted on 452 breast cancer patients who underwent surgery at Hanyang University Hospital, Seoul, South Korea. Data on clinicopathological characteristics including molecular pathologic markers were collected. Immunohistochemical staining of ASAP1 expression level were used to classify patients into high and low groups. In total, 452 cases low ASAP1 expression group was associated with significantly worse recurrence-free survival (p = 0.029). In ER-positive cases (n = 280), the low ASAP1 expression group was associated with significantly worse overall survival (p = 0.039) and recurrence-free survival (p = 0.029). In multivariate cox analysis, low ASAP1 expression was an independent significant predictor of poor recurrence-free survival in the overall patient group (hazard ratio = 2.566, p = 0.002) and ER-positive cases (hazard ratio = 4.046, p = 0.002). In the analysis of the TCGA dataset, the low-expression group of ASAP1 protein demonstrated a significantly poorer progression-free survival (p = 0.005). This study reports that low ASAP1 expression was associated with worse recurrence-free survival in invasive breast cancer.

Prognostic Implication of YY1 and CP2c Expression in Patients with Primary Breast Cancer.

Yin Yang 1 (YY1) is a transcription factor that regulates epigenetic pathways and protein modifications. CP2c is a transcription factor that functions as an oncogene to regulate cell proliferation. YY1 is known to interact with CP2c to suppress CP2c's transcriptional activity. This study aimed to investigate YY1 and CP2c expression in breast cancer and prognostic implications. In this study, YY1 and CP2c expression was evaluated using immunohistochemical staining, Western blot and RT-PCR assays. Of 491 patients with primary breast cancer, 138 patients showed YY1 overexpression. Luminal subtype and early stage were associated with overexpression (p < 0.001). After a median follow-up of 68 months, YY1 overexpression was found to be associated with a better prognosis (disease-free survival rates of 92.0% vs. 79.2%, p = 0.014). In Cox proportional hazards model, YY1 overexpression functioned as an independent prognostic factor after adjustment of hormone receptor/HER2 status and tumor size (hazard ratio of 0.50, 95% CI 0.26-0.98, p = 0.042). Quantitative analysis of YY1 and CP2c protein expression in tumors revealed a negative correlation between them. In conclusion, YY1 overexpression is a favorable prognostic biomarker in patients with breast cancer, and it has a negative correlation with CP2c at the protein level.

Robot-assisted Nipple Sparing Mastectomy: Recent Advancements and Ongoing Controversies.

Purpose of review: The purpose of this review is to summarize the recent technical advancements in RNSM, describe the ongoing teaching programs, and discuss the ongoing controversies. Recent findings: Robot-assisted nipple sparing mastectomy (RNSM) is the newest addition to the armamentarium of surgical techniques for patients who require a mastectomy. The potential benefits of using the da Vinci® Robotic Surgical System (Intuitive Surgical, Sunnyvale, CA) are the small 3D camera and lighting offering superior visualization, the Endowrist robotic instruments offering greater range of motion, and surgeon being at a seated position at the console rendering a more ergonomic operating position. Summary: RNSM can potentially help overcome the technical difficulties of performing a conventional NSM. Further studies are needed to elucidate the oncologic safety and cost-effectiveness of RNSM.

Prognostic Value of Neutrophil-to-Lymphocyte Ratio and Early Standardized Uptake Value Reduction in Patients With Breast Cancer Receiving Neoadjuvant Chemotherapy.

PURPOSE: We investigated the treatment response and prognosis using the neutrophil-to-lymphocyte ratio (NLR) and standardized uptake value (SUV) of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) in neoadjuvant settings. METHODS: Baseline NLR and maximum SUV (SUVmax) were retrospectively analyzed in 273 females with breast cancer who received neoadjuvant chemotherapy followed by surgery. Of these, 101 patients underwent 18F-FDG PET after 3-4 neoadjuvant chemotherapy cycles, which allowed the measurement of ΔSUVmax, an early reduction in SUVmax. NLR and early SUVmax reduction (ΔSUVmax) were classified as low and high, respectively, relative to the median values. RESULTS: The mean NLR was lower, and the mean ΔSUVmax was higher in patients with pathologic complete response (pCR) than in those with residual tumors. The ΔSUVmax was an independent variable associated with pCR. Furthermore, the high NLR group had poor recurrence-free survival (RFS) and overall survival. Among patients with ΔSUVmax data, high NLR (adjusted hazard ratio, 2.82; 95% confidence intervals [CI], 1.26-6.28; P = 0.016) and low ΔSUVmax (adjusted hazard ratio, 2.39; 95% CI, 1.07-5.34; P = 0.037) were independent prognostic factors for poor RFS. The categorization of the patients into four groups according to the combination of NLR and ΔSUVmax showed that patients with high NLR and low ΔSUVmax had significantly poorer RFS. CONCLUSION: Baseline NLR and ΔSUVmax were significantly associated with the prognosis of patients with breast cancer who received neoadjuvant chemotherapy. These results suggest that metabolic non-responders with defective immune systems have worse survival outcomes.

Survival benefit from axillary surgery in patients aged 70 years or older with clinically node-negative breast cancer: A population-based propensity-score matched analysis.

BACKGROUND: Older patients with breast cancer have good prognosis and most die from diseases other than breast cancer. Previous studies suggested that the surgical extent in older patients could be reduced. We aimed to compare survival outcomes in patients aged ≥70 years with clinically node-negative breast cancer, based on whether axillary surgery was performed. METHODS: A total of 2,995 patients with breast cancer aged ≥70 years who underwent breast surgery were included in the Korean Breast Cancer Registry. Patients were classified into two groups according to the performance of axillary surgery. We used propensity score matching for demographic and treatment factors to minimize selection bias. We compared the 5-year overall survival (OS) and breast cancer-specific survival (BCSS). RESULTS: Among 708 patients after 3:1 propensity score matching, 531 underwent breast surgery with axillary surgery and 177 underwent breast surgery alone. Of all patients, 51.7% had T1 stage, and 73.2% underwent mastectomy. Approximately 31.2% of patients received chemotherapy. Among patients who did not undergo axillary surgery, the 5-year OS and BCSS rates were 85.2% and 96.7%, respectively. The hazard ratio of axillary surgery for OS was 0.943 (95% confidence interval 0.652-1.365, p = 0.757), indicating no significant difference between two groups. CONCLUSIONS: Our study demonstrates that axillary surgery in a matched cohort of older patients with breast cancer and clinically negative nodes does not provide a survival benefit compared to patients undergoing breast surgery alone. These findings suggest that axillary surgery may be safely omitted in a select group of patients aged ≥70 years with clinically node-negative cancer. Further studies are needed to identify potential candidates for omitting axillary surgery.

Impact of the ACOSOG Z0011 trial on surgical practice in Asian patients: trends in axillary surgery for breast cancer from a Korean Breast Cancer Registry analysis.

BACKGROUND: Since the publication of the Z0011 trial, practice-changing clinical guidelines for breast surgery have been developed. Although recent studies confirmed the feasibility of the Z0011 strategy in Asian populations, there has been no study on the trends of axillary surgery in Asian cohort. This study aimed to investigate the time trend of axillary surgery for breast cancer from a Korean Breast Cancer Registry to understand the impact of the Z0011 trial in Asian patients. METHODS: We collected prospectively constructed data from the nationwide Korean Breast Cancer Registry (KBCR). We identified patients who underwent sentinel node biopsy followed by breast-conserving surgery from 2011 to 2018 and were found to have pathological stage T1-2N1-3M0 disease. Regression analyses were performed to compare the downward trend of axillary lymph node dissection (ALND) in Korean cohort with that previously reported in a Dutch cohort. RESULTS: From KBCR data, 7478 patients met the inclusion criteria. The proportion of ALND significantly decreased from 2011 (76.6%) to 2018 (47.5%). Multivariate analysis revealed that earlier years at diagnosis, larger tumor size, and lymphatic invasion were associated with a higher odds ratio of performing ALND. Compared to the Dutch cohort, the downward trend of ALND in Korea was significantly more gradual (annual percent change: 37.2 vs. 5.8%, p < 0.001). CONCLUSIONS: This study demonstrated a downward trend of ALND in Korean patients with breast cancer. However, the rate of decrease was significantly slower than that in the Dutch cohort.

Loss of Single-Stranded DNA Binding Protein 2 Expression Is Associated with Aggressiveness and Poor Overall Survival in Patients with Invasive Breast Carcinoma.

BACKGROUND: Single-stranded DNA binding protein 2 (SSBP2) is involved in the DNA damage response and the maintenance of genome stability. Previous studies have suggested that SSBP2 has a tumor suppressor function or oncogenic function. Loss of SSBP2 expression has been reported in various tumors. However, the role of SSBP2 expression in invasive breast carcinoma has not been reported. METHODS: Immunohistochemical staining for SSBP2 was performed on tissue microarrays consisting of 491 invasive breast carcinoma cases. The result of nuclear SSBP2 staining was stratified as either negative or positive. Then, we investigated the correlations between SSBP2 expression and various clinicopathological parameters and patient outcomes. RESULTS: Loss of nuclear SSBP2 expression was observed in 61 cases (12.4%) of 491 invasive breast carcinomas. Loss of nuclear SSBP2 expression was significantly correlated with larger tumor size (p < 0.001, chi-squared test), higher histological grade (p = 0.016, Cochran-Armitage trend test), higher pathological T stage (p < 0.001, Cochran-Armitage trend test), estrogen receptor status (p < 0.001, chi-squared test), and molecular subtype (p < 0.001, chi-squared test). Kaplan-Meier survival analysis revealed that patients with loss of nuclear SSBP2 expression had worse overall survival (p = 0.013, log-rank test). However, loss of nuclear SSBP2 expression was not correlated with recurrence-free survival (p = 0.175, log-rank test). CONCLUSIONS: Loss of nuclear SSBP2 expression was associated with adverse clinicopathological characteristics and poor patient outcomes. SSBP2 acts as a tumor suppressor in invasive breast carcinoma and may be used as a prognostic biomarker.

Associations between obesity, metabolic health, and the risk of breast cancer in East Asian women.

BACKGROUND: This study examined the associations between metabolic syndrome(MetS), obesity, their combination as a metabolic obesity phenotype, and the risk of breast cancer in East Asian postmenopausal women. METHODS: A total of 3,095,336 postmenopausal cancer-free women aged 40-79 years who underwent the National Health Insurance Service health examination between 2009 and 2010 were included. The incidence of invasive breast cancer was followed up until 2018. The presence of obesity (body mass index[BMI] ≥25 kg/m2), MetS, and each component of MetS was investigated. RESULTS: Obesity and MetS were associated with breast cancer risk, but when the effects of obesity and MetS were mutually adjusted, the associations were attenuated, especially for MetS. Only elevated fasting blood glucose levels and waist circumference increased the risk of breast cancer after adjusting for BMI. Compared to metabolically healthy normal-weight women, metabolically unhealthy normal-weight women, metabolically healthy obese, and metabolically unhealthy obese women had an increased risk of breast cancer. CONCLUSIONS: Obesity and MetS were independently associated with an increased risk of breast cancer in postmenopausal women, despite the relationship between MetS and breast cancer appearing to result from a partial association with BMI. Postmenopausal women should be encouraged to control their weight and metabolic health.

Axillary response according to neoadjuvant single or dual human epidermal growth factor receptor 2 (HER2) blockade in clinically node-positive, HER2-positive breast cancer.

Incorporating dual human epidermal growth factor receptor 2 (HER2) blockade into neoadjuvant systemic therapy (NST) led to higher response in patients with HER2-positive breast cancer. However, axillary response to treatment regimens, including single or dual HER2 blockade, in patients with clinically node-positive breast cancer remains uncertain. Our study aimed to examine the pathologic axillary response according to the type of NST, that is, single or dual HER2 blockade. In our study, 546 patients with clinically node-positive, HER2-positive breast cancer who received NST followed by axillary surgery were retrospectively selected and divided into three groups: chemotherapy alone, chemotherapy + trastuzumab and chemotherapy + trastuzumab with pertuzumab. The primary outcome was the axillary pathologic complete response (pCR). Among 471 patients undergoing axillary lymph node dissection, the axillary pCR rates were 43.5%, 74.5% and 68.8% in patients who received chemotherapy alone, chemotherapy + trastuzumab and chemotherapy + trastuzumab with pertuzumab, respectively. There was no difference in axillary pCR rates between patients who received single or dual HER2 blockade (P = .379). Among patients receiving chemotherapy + trastuzumab, patients without breast pCR had the greatest risk for residual axillary metastases (relative risk, 9.8; 95% confidence interval, 3.2-14.9; P < .0001). In conclusion, adding trastuzumab to chemotherapy increased the axillary pCR rate in patients with clinically node-positive, HER2-positive breast cancer; furthermore, dual HER2-blockade with trastuzumab and pertuzumab did not elevate the axillary response compared with trastuzumab alone. Breast pCR could be a strong predictor for axillary pCR in clinically node-positive patients treated with HER2-targeting therapy.

Relationship of the standard uptake value of 18F-FDG-PET-CT with tumor-infiltrating lymphocytes in breast tumors measuring ≥ 1 cm.

Evidence suggests that tumor cells and tumor-infiltrating lymphocytes (TILs) compete for glucose in the tumor microenvironment and that tumor metabolic parameters correlate with localized immune markers in several solid tumors. We investigated the relationship of the standardized uptake value (SUV) of 18F-fluorodeoxyglucose positron emission tomography computed tomography (18F-FDG-PET-CT) with stromal TIL levels in breast cancer. We included 202 patients who underwent preoperative 18F-FDG-PET-CT and had a tumor measuring ≥ 1 cm. Maximum SUV (SUVmax) was determined using 18F-FDG-PET-CT. Multiple logistic regression was used to identify factors related to high TIL levels (≥ 40%). All tumors were treatment naïve. A significant and weak correlation existed between continuous SUVmax and continuous TIL levels (p = 0.002, R = 0.215). Tumors with high SUVmax (≥ 4) had higher mean TIL levels than those with low SUVmax (< 4). In multivariable analysis, continuous SUVmax was an independent factor associated with high TIL levels; each 1-unit increment in SUVmax corresponded to an odds ratio of 1.14 (95% confidence interval: 1.01-1.29) for high TIL levels. Our study implies that SUV is associated with TILs in breast cancer and provides clinical evidence that elevated glucose uptake by breast tumors can predict the immune system-activated tumor micromilieu.

Validation of Clinical Treatment Score post-5 years (CTS5) risk stratification in premenopausal breast cancer patients and Ki-67 labelling index.

This study aimed to validate the Clinical Treatment Score post-5 years (CTS5)-based risk stratification in a cohort comprising pre- and postmenopausal patients with estrogen receptor (ER)-positive breast cancer. We investigated the clinicopathologic parameters including Ki-67 labelling index (LI) to identify factors affecting late distant recurrence (DR). Women with ER-positive breast cancer who were free of DR for 5 years were identified between January 2004 and December 2009. We investigated the risk of late DR (5-10 years) according to the CTS5 risk group. Cox regression analysis was used to determine the prognostic performance of CTS5 and identify factors associated with late DR. In all, 680 women were included. Of these, 379 (55.7%) were premenopausal and 301 (44.3%) were postmenopausal. At a median follow-up of 118 months, 32 women had late DR. CTS5 was a significant prognostic factor for late DR in both pre- and postmenopausal women. In the low CTS5 group, high Ki-67 LI (> 20%) was a significant risk factor for late DR. CTS5 is a useful tool for assessing the risk of late DR in pre- and postmenopausal women with ER-positive breast cancer. Extended endocrine therapy can be considered in patients with high Ki-67 LI (> 20%) in the low CTS5 group.

Local Treatment in Addition to Endocrine Therapy in Hormone Receptor-Positive and HER2-Negative Oligometastatic Breast Cancer Patients: A Retrospective Multicenter Analysis.

BACKGROUND: Recent trials have provided robust evidence demonstrating that endocrine therapy with/without targeted therapy, such as cyclin-dependent kinase 4/6 inhibitors or mTOR (mammalian target of rapamycin) inhibitors, effectively halts disease progression in hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer. We investigated the survival impact of local treatment of metastases as a first-line treatment after metastasis in HR-positive and HER2-negative breast cancer patients with a very low metastatic volume. MATERIALS AND METHODS: From a retrospectively constructed database for three institutes, we identified HR-positive and HER2-negative breast cancer patients with recurrent distant oligometastatic disease after initially curative treatment. De novo stage 4 patients were excluded, and only those with recurrent metastatic disease were included. Oligometastatic disease was defined as follows: (1) ≤2 metastatic lesions in a single organ, (2) a maximal diameter ≤3 cm, and (3) organ involvement, including the lung, liver, adrenal gland, bone, or distant lymph nodes. Local treatment comprised surgery or radiotherapy. Progression-free survival (PFS) and overall survival (OS) were investigated. RESULTS: Forty-nine patients were included; 33 underwent local treatment. Of these 33 patients, 5 underwent surgical resection and 27 received radiotherapy. One patient underwent both surgical resection and radiotherapy. Median PFS was significantly longer among the patients with local treatment than among the patients without local treatment (30.0 vs. 18.0 months, p = 0.049). In multivariate analysis, local treatment was shown to prolong PFS. However, median OS after metastasis did not differ with regard to local treatment (72.3 vs. 91.0 months, p = 0.272). CONCLUSION: We showed that local treatment could positively affect disease progression in HR-positive and HER2-negative oligometastatic breast cancer.

Comparison of resection margin status after single or double radiopaque marker insertion for tumor localization in breast cancer patients receiving neoadjuvant chemotherapy.

PURPOSE: Insertion of radiopaque markers is helpful for tumor localization in patients receiving neoadjuvant chemotherapy (NAC) followed by breast-conserving surgery (BCS). The aim of this retrospective study was to investigate the pathologic margin status in patients with single or double marker insertion. METHODS: We reviewed the records of 130 patients with marker insertion prior to NAC followed by BCS from January 2016 to September 2019. Under ultrasonography guidance, single or double markers were inserted to localize a tumor in the breast. The incidence of additional resection after frozen biopsy and re-excision after permanent pathologic diagnosis was analyzed. RESULTS: In a total of 130 patients, 104 had a single marker in the center of the tumor and 26 had double markers at the periphery of the tumor before NAC. Among 69 patients with residual invasive tumors after NAC, there was no difference in the additional resection rate after frozen biopsy (single vs. double markers; 14.3% vs. 38.5%, P = .059) or the re-excision rate after final pathologic diagnosis (0% vs. 7.7%, P = .188). After propensity score matching for tumor size and subtypes, the two groups showed no differences in the additional resection rate after frozen biopsy (7.7% vs. 19.2%, P = .139) or the re-excision rate (0% vs. 3.8%, P = .308). After a median follow-up of 19 months (range 8-48 months), local recurrence-free survival did not differ between the two groups (log-rank P = .456). CONCLUSIONS: Number of inserted markers for tumor localization did not affect the pathologic margin status after BCS.

Prognostic value of neutrophil-to-lymphocyte ratio in human epidermal growth factor receptor 2-negative breast cancer patients who received neoadjuvant chemotherapy.

We aimed to investigate the correlation between neutrophil-to-lymphocyte ratio (NLR) and pathologic complete response (pCR) and survival outcomes in human epidermal growth factor receptor 2 (HER2)-negative breast cancer patients who received neoadjuvant chemotherapy. The baseline NLR was evaluated in non-metastatic, HER2-negative breast cancer patients who received neoadjuvant chemotherapy. Baseline NLR was calculated as absolute neutrophil per lymphocyte count from pre-treatment blood samples. Any value ≥ 2.74 was considered to be a high NLR. In the 1,097 patients studied, 272 (24.4%) had high NLR and 825 (75.6%) had low NLR. The high NLR was an independent factor for pCR (OR 0.595; 95% CIs 0.398-0.890; P = 0.011). Furthermore, high NLR was a significant independent parameter affecting DFS (HR 2.298; 95% CIs 1.691-3.124; P < 0.001) and OS (HR 1.905; 95% CIs 1.167-3.108; P = 0.010). Regardless of the baseline NLR, survival outcomes were excellent in patients who achieved pCR, but high NLR was associated with worse survival for patients with residual invasive disease. Our study showed that NLR was predictive for treatment response and a prognostic factor in patients with HER2-negative breast cancer who received neoadjuvant chemotherapy. Moreover, we identified that high NLR was associated with poor survival outcomes in patients who did not achieve pCR.

Comparison of complications according to incision types in nipple-sparing mastectomy and immediate reconstruction.

BACKGROUND: Nipple-sparing mastectomy (NSM), followed by immediate reconstruction (IR) of the breast, has become a preferred surgical procedure with good cosmesis results and patient satisfaction. However, nipple-areolar complex (NAC) ischemia and necrosis remain major problems after NSM and IR. METHODS: We retrospectively analyzed patients who underwent NSM and IR at Gangnam Severance Hospital from January 2009 to June 2018. We compared the patient characteristics and complication rate among three different incisions (inframammary fold [IMF], radial, periareolar). Additionally, we identified the risk factors of NAC necrosis. RESULTS: Data from 290 eligible breasts in 275 patients were analyzed. Patients with IMF incision had relatively lower breast weights. The overall complication rate was the highest with periareolar incision and the lowest with IMF incision (42.6% vs. 18.8%, p < 0.001). The rate of NAC ischemia or necrosis was significantly different among the three incisions (9.7%, 17.0%, and 31.1% in IMF, radial, and periareolar, respectively; p < 0.001). Moreover, surgical treatments were more frequently needed in patients with periareolar incision. Periareolar incision, short distance from the tumor to the nipple base, and large breast weight were independent risk factors of NAC ischemia or necrosis in multivariable analysis. CONCLUSIONS: Compared with IMF incision, periareolar incision was associated with higher incidences of surgical complications and NAC necrosis. Careful consideration is needed when planning NSM in patients with a large breast volume or a tumor close to the nipple.

Radiotherapy-Induced High Neutrophil-to-Lymphocyte Ratio is a Negative Prognostic Factor in Patients with Breast Cancer.

Radiotherapy (RT) is the standard of care following breast-conserving operation in breast cancer patients. The neutrophil-to-lymphocyte ratio (NLR) reflects the systemic change caused as a result of the radiotherapy. We aimed to evaluate the association between RT and the change in NLR following the receipt of RT, and to investigate the prognostic impact. We retrospectively reviewed NLR values of breast cancer patients taken before the administration of the first and the last session of RT. The cut-off point for the NLR was determined using the Youden index and receiver operating characteristic (ROC) curve within the training set. Recurrence-free survival (RFS), distant metastasis free survival, and overall survival were the main outcomes. Patients with an NLR higher than 3.49 after RT were classified to an RT-induced high NLR group and showed a significantly higher recurrence rate compared to those with low NLR (p < 0.001). In a multivariate Cox proportional hazards model, RT-induced high NLR remained a significant prognostic factor (HR 2.194, 95% CI 1.230-3.912, p = 0.008 for tumor recurrence. We demonstrated that an increase in NLR over the course of RT has a negative impact on survival, putting these patients with RT-susceptible host immunity at a higher risk of tumor recurrence.

Significance of Non-Mass Enhancement in the Subareolar Region on Preoperative Breast Magnetic Resonance Imaging for Nipple-Sparing Mastectomy.

PURPOSE: The eligibility for nipple-sparing mastectomy (NSM) regarding subareolar non-mass enhancement (NME) on breast magnetic resonance imaging (MRI) was not clear. This study aimed to evaluate the eligibility for NSM according to the NME-to-nipple distance on preoperative breast MRI. METHODS: We identified patients with breast cancer who underwent mastectomy with NME suspected of malignancy in the subareolar region on preoperative breast MRI. The incidence of nipple invasion was pathologically evaluated according to the NME-to-nipple distance on breast MRI, and the clinicopathologic factors related to pathologic nipple invasion were analyzed. RESULTS: Of 137 patients, 55 (40.1%) had NME extension to the nipple, 53 (38.7%) had radiologic distance less than 2 cm, and 29 (21.2%) had radiologic distance of 2 cm or more. The rate of pathologic nipple invasion was 52.7% (29 of 55) in patients with NME extension to nipple, 7.5% (4 of 53) in patients with NME-to-nipple distance less than 2 cm, and 3.4% (1 of 29) in patients with NME-to-nipple distance of 2 cm or more (P < .001). NME extension to the nipple was an independent risk factor for pathologic nipple invasion (odds ratio 21.702; 95% confidence interval, 2.613-180.225; P = .004). The survival outcome was not different between NSM and conventional total mastectomy/skin-sparing mastectomy in patients with radiologic distance less than 2 cm, but without NME extension to the nipple. CONCLUSIONS: NSM is an acceptable procedure in patients with breast cancer with a low incidence of pathologic nipple invasion when there is no evidence of NME extension to the nipple on preoperative breast MRI.