Survival Comparisons between Breast Conservation Surgery and Mastectomy Followed by Postoperative Radiotherapy in Stage I-III Breast Cancer Patients: Analysis of the Surveillance, Epidemiology, and End Results (Seer) Program Database.

Background: This study aims to evaluate the overall and breast cancer-specific survival (BCSS) after breast-conserving surgery (BCS) plus radiotherapy (RT) compared with mastectomy plus RT in resectable breast cancer. Moreover, the aim is to also identify the subgroups who benefit from BCS plus RT and establish a predictive nomogram for stage II patients. Methods: Stage I−III breast cancer patients were identified from the Surveillance, Epidemiology, and End Results (SEER) database between 1990 and 2016. Patients with available clinical information were split into two groups: BCS plus RT and mastectomy plus RT. Kaplan−Meier survival analysis, univariate and multivariate regression analysis, and propensity score matching were used in the study. Hazard ratio (HR) was calculated based on stratified Cox univariate regression analyses. A prognostic nomogram by multivariable Cox regression model was developed for stage II patients, and consistency index (C-index) and calibration curve were used to evaluate the accuracy of the nomogram in the training and validation set. Results: A total of 24,590 eligible patients were enrolled. The difference in overall survival (OS) and BCSS remained significant in stage II patients both before and after PSM (after PSM: OS: HR = 0.8536, p = 0.0115; BCSS: HR = 0.7803, p = 0.0013). In stage II patients, the survival advantage effect of BCS plus RT on OS and BCSS was observed in the following subgroups: any age, smaller tumor size (<1 cm), stage IIA (T2N0, T0−1N1), ER (+), and any PR status. Secondly, the C-indexes for BCSS prediction was 0.714 (95% CI 0.694−0.734). The calibration curves showed perfect agreement in both the training and validation sets. Conclusions: BCS plus RT significantly improved the survival rates for patients of stage IIA (T2N0, T0−1N1), ER (+). For stage II patients, the nomogram was a good predictor of 5-, 10-, and 15-year BCSS. Our study may help guide treatment decisions and prolong the survival of stage II breast cancer patients.

Survival With Surgery Is Superior to Survival Without Surgery in Breast Cancer Patients Aged 85 years or Older: A Retrospective Study.

BACKGROUND: Surgical treatment of breast cancer patients aged 85 years or older is still controversial. METHODS: A series of surgically treated breast cancer patients aged 85 years or older was evaluated. The clinicopathological features and outcomes of these patients were compared with the features and outcomes of breast cancer patients in the same age group who were managed without surgery. RESULTS: A total of 45 patients (75%) received surgical treatment, and 15 patients (25%) were managed without surgery. Significantly more patients treated by surgery underwent systemic treatment than patients managed without surgery (P = .003). The 5-year disease-free survival rate of patients treated by surgery was 80.7% (95% confidence interval: 66.2-98.5%), which was significantly higher than that of the patients managed without surgery (P = .001). CONCLUSIONS: The surgical treatment of breast cancer patients aged 85 years or older is warranted. This outcome was achieved with the use of hormonal therapy.

The reliability of breast cancer surgery in a regional pandemic hospital during the COVID-19 pandemic: Delay or Do?

PURPOSE: The purpose of this study was to examine the effect of COVID-19 infection on the morbidity and mortality rates of breast cancer patients performed in the East Mediterranean region of Turkey during the COVID-19 pandemic and to share the results of those investigations. METHODS: This retrospective study included all breast cancer patients that underwent surgery during the COVID-19 pandemic in the General Surgery Clinic of Adana City Training and Research Hospital, a regional pandemic hospital, between March 11, 2020 and December 25, 2020. The patients were evaluated preoperatively and postoperatively (the first 30 days) in terms of COVID-19 infection. Moreover, these patients were also evaluated in terms of admission to the hospital, length of hospital stay, and mortality due to COVID-19 infection during the follow-up period of the study. RESULTS: Included in the study were 139 patients that underwent surgery for breast cancer during the pandemic period, with no observed mortality or morbidity associated with COVID-19 in any patient postoperatively within the first 30 days. In addition, within 121.22±70.05 days, the mean and standard deviation of the study's follow-up period, 19 patients (15.7%) were admitted to the hospital with a suspected COVID-19 infection (after the first 30 days postoperatively) and 6 of them (4.3%) returned a positive PCR test. All of the COVID-19 positive patients (6 patients, 4.3%) were hospitalised and 3 of them (2.2%) died due to the COVID-19 infection. CONCLUSION: Breast cancer surgery can be performed safely during the COVID-19 pandemic period after taking the necessary precautions.

Survival benefit of a combined surgical approach in patients with metastatic breast cancer.

BACKGROUND: We previously reported survival benefit of surgery in patients with stage IV breast cancer (BC); prospective trials yielded inconclusive results. METHODS: We sampled the National Cancer Database (2004-2016) for de novo stage IV BC patients undergoing both primary site resection and metastasectomy. A multivariate Cox-regression survival model investigated the overall survival (OS) of this surgical approach as compared to lumpectomy/mastectomy alone, metastasectomy alone, or no surgery. The Kaplan-Meier method was used to demonstrate the utility of surgery when metastasis were confined to 1 site stratifying by tissue type. RESULTS: A total of n = 55,125 patients were included. As compared to lumpectomy/mastectomy alone (43 months), lumpectomy/mastectomy + metastasectomy exhibited the best OS (50 months, p = 0.012), metastasectomy alone showed slightly worse OS (30 months, p < 0.0001), and no surgery had the worst OS (21 months, p < 0.0001). In metastasis confined to 1 site, superior OS with combined lumpectomy/mastectomy and metastasectomy versus lumpectomy/mastectomy alone was observed with liver (72.8 vs. 48.1 months, p < 0.001) or lung (49.2 vs. 36.8 months, p < 0.001) metastasis but not bone (52.2 vs. 49.9 months, p < 0.001) or brain (16.2 vs. 15.5 months, p < 0.001). CONCLUSION: Patients with metastatic BC undergoing primary site resection and metastasectomy exhibited optimal OS, particularly when metastasis involved only the liver or lung.

Rates of Ipsilateral Local-regional Recurrence in High-risk Patients Undergoing Immediate Post-mastectomy Reconstruction (AFT-01).

BACKGROUND: Some surgeons remain hesitant to perform immediate breast reconstruction (IBR) in patients with higher risk cancers owing to concerns about cancer recurrence and/or detection. Our objective was to determine the rate of ipsilateral local-regional recurrence for stage II/III patients who underwent IBR. METHODS: The National Cancer Database special study mechanism was used to create a stratified sample of women diagnosed with stage II/III breast cancer from 1217 facilities. Demographic, tumor, and recurrence data for women who underwent mastectomy with or without IBR were abstracted, including location of recurrence and method of detection. Estimates of 5-year local-regional recurrence rates were calculated and factors associated with recurrence were identified with multivariable Cox regression. RESULTS: Some 13% (692/5318) of stage II/III patients underwent IBR after mastectomy. Patients undergoing IBR were younger (P < .001), with fewer comorbid conditions (P < .001), and with lower tumor burden in the breast (P = .001) and the lymph nodes (P = 0.01). The 5-year rate of ipsilateral local-regional recurrence was 3.6% with no significant difference between patients with or without IBR (3.0% vs. 3.7%, P = .4). Most recurrences were detected by the patient (45%) or on physician examination (24%). Reconstruction was not associated with recurrence on multivariable analysis (hazard ratio = 0.83, P = .52). CONCLUSION: Women with stage II/III breast cancer selected for IBR had similar rates of ipsilateral local-regional recurrence compared with those undergoing mastectomy alone. Offering IBR after mastectomy in a patient-centered manner to select patients with stage II/III breast cancer is an acceptable consideration.

Lumpectomy followed by radiation improves survival in HER2 positive and triple-negative breast cancer with high tumor-infiltrating lymphocytes compared to mastectomy alone.

OBJECTIVE: The goal was to compare the 5-year DFS and 5-year OS in patients with early-stage human epidermal growth factor receptor 2 breast cancer (HER2+ BC) and triple-negative breast cancer (TNBC) in relation to the amount of stromal tumor-infiltrating lymphocytes (TILs) after locoregional management by either mastectomy without radiation or lumpectomy and whole-breast radiotherapy (RT). METHODS: This was a retrospective review of HER2+ BC and TNBC patients' charts and histopathology slides with clinical stage of T1-T2 N0 who presented at our facility between January 2009 and December 2019. Locoregional treatment included either mastectomy without RT (M) or lumpectomy with RT (L+R). TILs were assessed by three pathologists using the guidelines of the 2014 TILs working group. A competing risk model and Kaplan-Meier analysis were used to analyze correlations between TILs levels and clinical outcome. RESULTS: We reviewed 211 patients' charts. Of them, 190 proceeded to the final analysis. Patients were split into groups of "low TILs" and "high TILs" based on a 50% TILs cut-off. Of them 26% had high TILs, 48% received RT, 97% received chemotherapy, all HER2+ BC patients received HER2-directed therapy and all HER2+ BC that were also hormone receptor positive (HR+) received endocrine therapy (ET). In patient with low TILs, L+R did not improve outcomes compared to M. Moreover, patients with high TILs had a significant improvement of their DFS and OS with L+R when compared to M. CONCLUSION: The results of our study reflect that a selected group of HER2+ BC and TNBC with elevated TILs, L+R is associated with improvement of 5-year DFS and 5-year OS.

Cost-Effectiveness Modeling of Surgery Plus Adjuvant Endocrine Therapy Versus Primary Endocrine Therapy Alone in UK Women Aged 70 and Over With Early Breast Cancer.

OBJECTIVES: Approximately 20% of UK women aged 70+ with early breast cancer receive primary endocrine therapy (PET) instead of surgery. PET reduces surgical morbidity but with some survival decrement. To complement and utilize a treatment dependent prognostic model, we investigated the cost-effectiveness of surgery plus adjuvant therapies versus PET for women with varying health and fitness, identifying subgroups for which each treatment is cost-effective. METHODS: Survival outcomes from a statistical model, and published data on recurrence, were combined with data from a large, multicenter, prospective cohort study of over 3400 UK women aged 70+ with early breast cancer and median 52-month follow-up, to populate a probabilistic economic model. This model evaluated the cost-effectiveness of surgery plus adjuvant therapies relative to PET for 24 illustrative subgroups: Age {70, 80, 90} × Nodal status {FALSE (F), TRUE (T)} × Comorbidity score {0, 1, 2, 3+}. RESULTS: For a 70-year-old with no lymph node involvement and no comorbidities (70, F, 0), surgery plus adjuvant therapies was cheaper and more effective than PET. For other subgroups, surgery plus adjuvant therapies was more effective but more expensive. Surgery plus adjuvant therapies was not cost-effective for 4 of the 24 subgroups: (90, F, 2), (90, F, 3), (90, T, 2), (90, T, 3). CONCLUSION: From a UK perspective, surgery plus adjuvant therapies is clinically effective and cost-effective for most women aged 70+ with early breast cancer. Cost-effectiveness reduces with age and comorbidities, and for women over 90 with multiple comorbidities, there is little cost benefit and a negative impact on quality of life.

Operable breast cancer: How not to worsen the prognosis, especially in triple negative and stage II tumors.

INTRODUCTION: Oncological surgery must follow some fundamental principles to be truly curative, one of which is the resection of the tumor with surgical margins free of neoplasia. In breast cancer, surgery with positive margins should be expanded immediately. There are probably different intensities, between the stages and molecular subtypes of operable breast cancer, of worsening prognosis due to the surgical margin compromised by the neoplasia in women not submitted to the necessary enlargement of the positive surgical margin. MATERIALS AND. METHODS: Seven hundred and forty-seven women with invasive ductal carcinoma of the breast, analyzing anatomical-pathological information, types of surgery, molecular subtypes, and the presence or absence of the surgical margin compromised by neoplasia. RESULTS: Sixty-one (8.2%) patients had positive surgical margin, causing 2.85 times more risk of locoregional relapse compared to negative surgical margin by multivariate analysis. In subgroup analysis, among stages I, II and III, stage II was the most negatively impacted, with those patients presenting 2.42 times more risk of distant metastasis and 4.94 times more risk of locoregional relapses compared to negative surgical margin by multivariate analysis. Among the molecular subtypes, Triple Negative tumors with a positive surgical margin had 3.56 times more risk of death, 4.98 times more risk of distant metastasis and 5.55 times more risk of locoregional relapse compared to negative surgical margin by multivariate analysis. CONCLUSIONS: The positive surgical margin, especially in Stage II and Triple-Negative breast cancer patients negatively impact the patient's evolution, increasing risk of distant metastasis and death.

Additional radiotherapy to breast-conserving surgery is an optional treatment for de novo stage IV breast cancer: A population-based analysis.

BACKGROUND: We aim to assess the value of locoregional treatment (LRT) including breast-conserving surgery (BCS), mastectomy (MAST), and radiotherapy (RT) in patients with de novo stage IV breast cancer. METHODS: Patients with de novo stage IV breast cancer were retrospectively identified from the Surveillance, Epidemiology, and End Results database between 2004 and 2014. Kaplan-Meier analysis, log-rank tests, propensity score matching (PSM), and the multivariate Cox proportional model were used for statistical analysis. RESULTS: A total of 5798 patients were identified including 849 (14.6%), 763 (13.2%), 2338 (40.3%), and 1848 (31.9%) who received BCS alone, BCS+RT, MAST alone, and MAST+RT, respectively. The proportions of receiving BCS decreased from 35.9% in 2004 to 26.2% in 2014 (p = 0.002), and the probability of patients receiving MAST increased from 64.1% in 2004 to 74.8% in 2014 (p = 0.002). Before PSM, there was a significant difference in breast cancer-specific survival (BCSS) among the treatment arms. Patients who received RT had better BCSS, the 5-year BCSS was 40.5%, 52.3%, 41.5%, and 47.7% in patients treated with BCS alone, BCS+RT, MAST alone, and MAST+RT, respectively (p < 0.001). In the PSM cohort, patients treated with BCS alone had lower 5-year BCSS compared to those treated with BCS+RT (43.9% and 52.1%, p = 0.002). However, there were comparable 5-year BCSS between BCS+RT and MAST alone groups (51.3% and 50.1%, p = 0.872), and BCS+RT and MAST+RT cohorts (51.5% and 55.7%, p = 0.333). Similar results were confirmed in multivariate analysis. CONCLUSIONS: Postoperative RT improves BCSS in patients with de novo stage IV breast cancer, and BCS+RT shows a non-inferior outcome compared to MAST+RT. BCS+RT may be the optimal local management of de novo stage IV breast cancer.

Survival from breast cancer in women with a BRCA2 mutation by treatment.

BACKGROUND: The impact of various breast-cancer treatments on patients with a BRCA2 mutation has not been studied. We sought to estimate the impact of bilateral oophorectomy and other treatments on breast cancer-specific survival among patients with a germline BRCA2 mutation. METHODS: We identified 664 women with stage I-III breast cancer and a BRCA2 mutation by combining five different datasets (retrospective and prospective). Subjects were followed for 7.2 years from diagnosis to death from breast cancer. Tumour characteristics and cancer treatments were patient-reported and derived from medical records. Predictors of survival were determined using Cox proportional hazard models, adjusted for other treatments and for prognostic features. RESULTS: The 10-year breast-cancer survival for ER-positive patients was 78.9% and for ER-negative patients was 82.3% (adjusted HR = 1.23 (95% CI, 0.62-2.45, p = 0.55)). The 10-year breast-cancer survival for women who had a bilateral oophorectomy was 89.1% and for women who did not have an oophorectomy was 59.0% (adjusted HR = 0.45; 95% CI, 0.28-0.72, p = 0.001). The adjusted hazard ratio for chemotherapy was 0.83 (95% CI, 0.65-1.53: p = 0.56). CONCLUSIONS: For women with breast cancer and a germline BRCA2 mutation, positive ER status does not predict superior survival. Oophorectomy is associated with a reduced risk of death from breast cancer and should be considered in the treatment plan.

Metaplastic breast cancer: Prognostic and therapeutic considerations.

INTRODUCTION: Metaplastic breast cancer (MBC) is a rare condition of breast tumor with different subtypes, considered a disease with worse prognosis; treatments and survival are often unclear and conflicting. METHODS: We consecutively collected 153 primary MBCs of different subtypes. Breast surgery, neoadjuvant or adjuvant treatment, clinic-pathological factors, number and type of events during follow-up were considered to evaluate overall survival (OS) and invasive disease-free survival (IDFS). RESULTS: The majority of MBC was triple-negative (TN) subtype (88.7%), G3 (95.3%), pN0 (70.6%), and with high levels of Ki-67 (93.5%). For OS and IDFS, no significant associations were seen between the different MBC subtypes. The matched triple-negative MBC (TNMBC) and ductal TNBC cohorts had similar prognosis both in terms of OS (p = .411) and IDFS (p = .981). We observed a positive trend for TNMBC patients treated in the adjuvant setting with the cyclofosfamide, methotrexate, 5-fluorouracil protocol for better OS (p = .090) and IDFS (p = .087). A poor or absent response rate was observed in the neoadjuvant setting. CONCLUSION: Our results demonstrate that metaplastic and ductal breast cancers with TN phenotype are similar in terms of overall and disease-free survival. Metaplastic cancers are poorly responsive to neoadjuvant treatment, and in the absence of novel targeted therapies, surgical treatment remains the first choice.

Leveraging the increased rates of pathologic complete response after neoadjuvant treatment in breast cancer to de-escalate surgical treatments.

INTRODUCTION: Breast conservative surgery (BCS) and sentinel lymph node biopsy (SLNB) after neoadjuvant treatment (NAT) is safe and effective for selected patients. This aim of this study is to evaluate the impact of anatomic site of response on outcomes and to assess the real population who may benefit from nonsurgical approaches after NAT. MATERIAL AND METHODS: From a prospectively maintained database, patients with T1-4 N0-2 breast cancer undergoing NAT were identified. Clinicopathological and survival rates were compared in relation to response and anatomic site of response. RESULTS: Six hundred and forty-six patients were included in the study. Pathologic complete response (pCR) was an independent factor for BCS and SLN. HER2 positive and TN tumors with cN0 achieving a breast pCR remain ypN0 (p = .002). Residual axillary disease was associated with breast residual tumor (p = .05) and subtype (p = .001). With a median follow up of 35.25 months, patients with any pCR had improved survival when compared with partial response, but not significant differences between pCR, axillary pCR, or breast pCR. CONCLUSION: Achieving a pCR increases BCS and SLN. In selected subgroups, sparing any axillary surgery after NAT maybe feasible. In cN+ patients, any pCR was associated with survival, but not the anatomic site of response.

Intraoperative opioids are associated with improved recurrence-free survival in triple-negative breast cancer.

BACKGROUND: Opioid-induced immunomodulation may be of particular importance in triple-negative breast cancer (TNBC) where an immune response is associated with improved outcome and response to immunotherapy. We evaluated the association between intraoperative opioids and oncological outcomes and explored patterns of opioid receptor expression in TNBC. METHODS: Consecutive patients with stage I-III primary TNBC were identified from a prospectively maintained database. Opioid receptor expression patterns in the tumour microenvironment were analysed using publicly available bulk and single-cell RNA-seq data. RESULTS: A total of 1143 TNBC cases were retrospectively analysed. In multivariable analysis, higher intraoperative opioid dose was associated with favourable recurrence-free survival, hazard ratio 0.93 (95% confidence interval 0.88-0.99) per 10 oral morphine milligram equivalents increase (P=0.028), but was not significantly associated with overall survival, hazard ratio 0.96 (95% confidence interval 0.89-1.02) per 10 morphine milligram equivalents increase (P=0.2). Bulk RNA-seq analysis of opioid receptors showed that OPRM1 was nearly non-expressed. Compared with normal breast tissue OGFR, OPRK1, and OPRD1 were upregulated, while TLR4 was downregulated. At a single-cell level, OPRM1 and OPRD1 were not detectable; OPRK1 was expressed mainly on tumour cells, whereas OGFR and TLR4 were more highly expressed on immune cells. CONCLUSIONS: We found a protective effect of intraoperative opioids on recurrence-free survival in TNBC. Opioid receptor expression was consistent with a net protective effect of opioid agonism, with protumour receptors either not expressed or downregulated, and antitumour receptors upregulated. In this era of personalised medicine, efforts to differentiate the effects of opioids across breast cancer subtypes (and ultimately individual patients) should continue.

Salvage Mastectomy Versus Second Conservative Treatment for Second Ipsilateral Breast Tumor Event: A Propensity Score-Matched Cohort Analysis of the GEC-ESTRO Breast Cancer Working Group Database.

PURPOSE: Second conservative treatment has emerged as an option for patients with a second ipsilateral breast tumor event after conserving surgery and breast irradiation. We aimed to address the lack of evidence regarding second breast event treatment by comparing oncologic outcomes after conservative treatment or mastectomy. METHODS AND MATERIALS: Oncologic outcomes were analyzed using a propensity score-matched cohort analysis study on patients who received a diagnosis of a second breast event between January 1995 and June 2017. Patient data were collected from 15 hospitals/cancer centers in 7 European countries. Patients were offered mastectomy or lumpectomy plus brachytherapy. Propensity scores were calculated with logistic regression and multiple imputations. Matching (1:1) was achieved using the nearest neighbor method, including 10 clinical/pathologic data related to the second breast event. The primary endpoint was 5-year overall survival from the salvage surgery date. Secondary endpoints were 5-year cumulative incidence of third breast event, regional relapse and distant metastasis, and disease-free and specific survival. Complications and 5-year incidence of mastectomy were investigated in the conservative treatment cohort. RESULTS: Among the 1327 analyzed patients (mastectomy, 945; conservative treatment, 382), 754 were matched by propensity score (mastectomy, 377; conservative treatment, 377). The median follow-up was 75.4 months (95% confidence interval [CI], 65.4-83.3) and 73.8 months (95% CI, 67.5-80.8) for mastectomy and conservative treatment, respectively (P = .9). In the matched analyses, no differences in 5-year overall survival and cumulative incidence of third breast event were noted between mastectomy and conservative treatment (88% [95% CI, 83.0-90.8] vs 87% [95% CI, 82.1-90.2], P = .6 and 2.3% [95% CI, 0.7-3.9] vs 2.8% [95% CI, 0.8-4.7], P = .4, respectively). Similarly, no differences were observed for all secondary endpoints. Five-year cumulative incidence of mastectomy was 3.1% (95% CI, 1.0-5.1). CONCLUSIONS: To our knowledge, this is the largest matched analysis of mastectomy and conservative treatment combining lumpectomy with brachytherapy for second breast events. Compared with mastectomy, conservative treatment does not appear to be associated with any differences in terms of oncologic outcome. Consequently, conservative treatment could be considered a viable option for salvage treatment.

Machine learning to predict the cancer-specific mortality of patients with primary non-metastatic invasive breast cancer.

PURPOSE: We used five machine-learning algorithms to predict cancer-specific mortality after surgical resection of primary non-metastatic invasive breast cancer. METHODS: This study was a secondary analysis of data for 1661 women with primary non-metastatic invasive breast cancer. The overall patient population was divided into a training group and a test group at a ratio of 8:2 and python was used for machine learning to establish the prognosis model. RESULTS: The machine-learning Gbdt algorithm for cancer-specific death caused by various factors showed the five most important factors, ranked from high to low as follows: the number of regional lymph node metastases, LDH, triglyceride, plasma fibrinogen, and cholesterol. Among the five algorithm models in the test group, the highest accuracy rate was by DecisionTree (0.841), followed by the gbm algorithm (0.838). Among the five algorithms, the AUC values from high to low were GradientBoosting (0.755), gbm (0.755), Logistic (0.733), Forest (0.715), and DecisionTree (0.677). CONCLUSION: Machine learning can predict cancer-specific mortality after surgery for patients with primary non-metastatic invasive breast.

Clinical outcomes of patients with ductal carcinoma in situ in Hong Kong: 10-year territory-wide cancer registry study.

BACKGROUND: Incidence of ductal carcinoma in situ (DCIS) has increased in recent decades because of breast cancer screening. This study comprised a long-term survival analysis of DCIS using 10-year territory-wide data from the Hong Kong Cancer Registry. METHODS: This study included all patients diagnosed with DCIS in Hong Kong from 1997 to 2006. Exclusion criteria were age <30 years or ≥70 years, lobular carcinoma in situ, Paget's disease, and co-existing invasive carcinoma. Patients were stratified into those diagnosed from 1997 to 2001 and those diagnosed from 2002 to 2006. The 5- and 10-year breast cancer-specific survival rates were evaluated; standardised mortality ratios were calculated. RESULTS: Among the 1391 patients in this study, 449 were diagnosed from 1997 to 2001, and 942 were diagnosed from 2002 to 2006. The mean age at diagnosis was 49.2±9.2 years. Overall, 51.2% of patients underwent mastectomy and 29.5% received adjuvant radiotherapy. The median follow-up interval was 11.6 years; overall breast cancer-specific mortality rates were 0.3% and 0.9% after 5 and 10 years of follow-up, respectively. In total, 109 patients (7.8%) developed invasive breast cancer after a considerable delay. Invasive breast cancer rates were comparable between patients diagnosed from 1997 to 2001 (n=37, 8.2%) and those diagnosed from 2002 to 2006 (n=72, 7.6%). CONCLUSION: Despite excellent long-term survival among patients with DCIS, these patients were more likely to die of breast cancer, compared with the general population of women in Hong Kong.

Prognosis of selected triple negative apocrine breast cancer patients who did not receive adjuvant chemotherapy.

BACKGROUND: Triple negative breast cancer encompasses several biological entities with different outcomes and is a priority to identify which patients require more treatment to reduce the risk of recurrence and which patients need less treatment. PATIENTS AND METHODS: Among the 210 women with first primary invasive apocrine non metastatic breast cancer operated on between January 1998 and December 2016 at the European Institute Oncology, Milan, we identified 24 patients with a pT1-pT2, node-negative, triple negative subtype and Ki-67 ≤ 20% who did not receive adjuvant chemotherapy (CT). We compared the outcome of this cohort with a similar group of 24 patients with ductal tumors who received adjuvant chemotherapy, matched by pathological stage and biological features and also with a similar group of 12 patients with apocrine tumors who received adjuvant chemotherapy. RESULTS: The median age was 64 and 61 years in the apocrine (w/o CT) and ductal group, respectively. The median value of Ki-67 expression was 12% in the apocrine group (w/o CT) and 16% in the ductal group (p < 0.001). After a median follow-up of 7.5 years, no patients in the apocrine group (w/o CT) experienced a breast cancer related event compared with 4 events in the ductal carcinoma group (Gray test p-value = 0.11). CONCLUSIONS: The outcome of selected apocrine triple negative breast cancer patients who did not received adjuvant chemotherapy is excellent and supports a treatment de-escalation. Multicenter projects focusing on the possibility of avoiding adjuvant chemotherapy in selected subtypes of triple negative breast cancers with favorable outcome are warranted.

Prognostic Role of Immune Markers in Triple Negative Breast Carcinoma.

Tumor immune microenvironment (TIME) is a significant prognostic parameter for triple negative breast carcinomas (TNBC) due to being a target for immunotherapeutic agents and its essential role during the cancer immunoediting process. In this study, CD8, FOXP3, CD163, PD-L1/SP142 and PD-L1/SP263 antibodies were examined in a sample of 51 TNBC cases. Patients who received neoadjuvant therapy were excluded. CD8, FOXP3 and CD163 antibodies were evaluated separately in intratumoral area (ITA) and tumor stroma (TS). PD-L1 status was also examined in tumor cells (TC) and immune cells (IC) using both SP142 and SP263 antibodies. In multivariate Cox regressions, the only antibody that was found to be significantly associated with survival was SP142. SP142-positivity in TC and IC was related to increased overall survival. Higher CD163 expression in ITA and SP263-positivity in IC were associated with younger age. Lymphatic/angioinvasion was more frequent in cases with negative/low CD8 and FOXP3 expressions. Moreover, metastatic axillary lymph node(s) was associated with negative/low FOXP3 expression in TS. CD8, FOXP3, CD163, SP142 and SP263 expressions were positively correlated with each other, except a mild discordance caused by CD163 in ITA. Although PD-L1 status with both SP142 and SP263 antibodies were concordant in the majority of cases, 33.3% and 13.7% of the cases showed SP142-negative/SP263-positive pattern in TC and IC respectively. In conclusion, we suggest that composition, density and localization of the immune cells and the check point molecules are important prognostic parameters in TNBC. Immunohistochemistry can be used as an accessible and less expensive tool to demonstrate TIME.

Influence of adherence with guideline-driven recommendations on survival in women operated for breast cancer: Real-life evidence from Italy.

BACKGROUND: A set of indicators to assess the quality of care for women operated for breast cancer was developed by an expert working group of the Italian Health Ministry in order to compare the Italian regions. A study to validate these indicators through their relationship with survival was carried out. METHODS: The 16,753 women who were residents in three Italian regions (Lombardy, Emilia-Romagna and Lazio) and hospitalized for breast cancer surgery during 2011 entered the cohort and were followed until 2016. Adherence to selected recommendations (i.e., surgery timeliness, medical therapy timeliness, appropriateness of complementary radiotherapy and mammographic follow-up) was assessed. Multivariable proportional hazards models were fitted to estimate hazard ratios for the association between adherence with recommendations and the risk of all-cause mortality. RESULTS: Adherence to recommendations was 53% for medical therapy timeliness, 73% for appropriateness of mammographic follow-up, 74% for surgery timeliness and 82% for appropriateness of complementary radiotherapy. Risk reductions of 26%, 62% and 56% were observed for adherence to recommendations on medical therapy timeliness, appropriateness of complementary radiotherapy and mammographic follow-up, respectively. There was no evidence that mortality was affected by surgery timeliness. CONCLUSIONS: Clinical benefits are expected from improvements in adherence to the considered recommendations. Close control of women operated for breast cancer through medical care timeliness and appropriateness of radiotherapy and mammographic monitoring must be considered the cornerstone of national guidance, national audits, and quality improvement incentive schemes.

Association of surgical margins with local recurrence in patients undergoing breast-conserving surgery after neoadjuvant chemotherapy.

BACKGROUND: The aim of the current study was to report a single-institution experience using breast-conserving surgery after neoadjuvant chemotherapy (NACT), focusing on the association between microscopic resection margin status and locoregional recurrence (LRR). METHODS: Our institutional prospectively maintained database was reviewed to identify patients who were treated with NACT between January 2008 and April 2018. RESULTS: Among the main partial mastectomy specimens available for analysis (n = 161), 28 had margins < 1 mm, 21 had margin width of 1-2 mm and the remaining 112 had margins > 2 mm. LRR occurred in 16 patients (9.9%) and distant metastases were detected in 27 (16.8%) patients. There was no significant difference in the LRR between the > 2 mm margin group with a 60-month cumulative survival of 85.2% compared with 76.2% for the ≤2 mm group (P = 0.335) in the Kaplan-Meier analysis. When we stratified patients by margin widths of ≥1 mm or <  1 mm, there was no LRR-free survival benefit observed for the ≥1 mm pathologic excision margin group in the univariate analysis (hazard ratio = 0.443; 95% confidence interval = 0.142-1.383; P = 0.161) with a 60-month cumulative LRR-free survival of 84.9% compared with 69.5% for the < 1 mm margin cohort (P = 0.150). CONCLUSIONS: In the absence of multiple scattered microscopic tumour foci, a negative margin of no ink on tumour maybe sufficient for stage I-III invasive breast cancer treated with NACT and breast-conserving surgery.