Analysis of breast cancer survival in a northeastern Brazilian state based on prognostic factors: A retrospective cohort study.

Breast cancer is a major health problem worldwide. Analysis of breast cancer epidemiology in emerging countries enables assessment of prognostic factors, cancer care quality, and the equity of resource distribution. We aimed to estimate the overall (OS) and cancer-specific survival (SS) of breast cancer patients in the northeastern Brazilian state of Sergipe to identify independent prognostic factors. We analyzed a cohort for the factors age at diagnosis, place of residence, time to treatment, staging, and molecular classification, using the Kaplan-Meier method, log-rank test, Pearson's chi-squared test and Cox regression model. The outcome was the vital status at the end of the study. Our analysis showed an OS probability of 0.72 and an SS probability of 0.75. In multivariate analysis, time to treatment within 60 days, stage IV, and triple-negative classification remained independent prognostic factors for both OS [unadjusted hazard ratio (HRp) 1.50 (1.21; 1.86), HRp 16.56 (8.35; 32.85), and HRp 2.73 (1.73; 4.29), respectively] and SS [HRp 1.43 (1.13; 1.81), HRp 20.53 (9.45; 44.56), and HRp 3.14 (1.88; 5.26), respectively]. Better survival was demonstrated for the following patients: those receiving their first treatment after 60 days, with an OS of 52.5 months (51.2; 53.8) and SS of 53.5 months (52.3; 54.7); stage I patients, with an OS of 58.8 months (57.7; 60.0) and SS of 59.2 months (58.1; 60.3); patients without nodal metastasis, with an OS of 54.2 months (53.0; 55.4) and SS of 55.6 months (54.5; 56.7); and patients with luminal A classification, with an OS of 56.8 months (55.0; 58.5) and SS of 57.8 months (56.2; 59.4). This study identified independent prognostic factors and that OS and SS were lower for patients from Sergipe than for patients in high-income areas. Therefore, determining the profiles of breast cancer patients in this population will inform specific cancer care.

Survival analysis in patients with invasive lobular cancer and invasive ductal cancer according to hormone receptor expression status in the Korean population.

BACKGROUND: We compared the clinicopathological characteristics and survival outcomes of invasive lobular carcinoma (ILC) cases with those of invasive ductal carcinoma (IDC) cases in various hormone receptor expression subgroups. METHODS: We compared clinicopathological characteristics, overall survival (OS), and breast cancer-specific survival (BCSS) between patients with IDC (n = 95,486) and ILC (n = 3,023). In addition, we analyzed the effects of different hormone receptor expression subgroups on survival. RESULTS: The ILC group had more instances of advanced stage and hormonal receptor positivity than did the IDC group (p < 0.001), but the IDC group had higher histological grade and nuclear grade, as well as higher frequency of human epidermal growth factor receptor 2 and Ki67 expression than did the ILC group (p < 0.001). The OS and BCSS were not significantly different between the IDC and ILC groups. The 5-year OS of the IDC group was 88.8%, while that of the ILC group was 90.6% (p = 0.113). The 5-year BCSS of the IDC group was 94.8%, while that of the ILC group was 95.0% (p = 0.552). When analyzing each hormone receptor expression subgroup, there were no significant differences in survival between the IDC and ILC groups. However, the estrogen receptor (ER) negative/progesterone receptor (PR) negative subgroup showed differences in survival between the IDC and ILC groups. Moreover, the hazard ratio of ILC in the ER negative/PR negative subgroup was 1.345 (95% confidence interval: 1.012-1.788; p = 0.041). CONCLUSIONS: Hormone receptor expression should be considered when determining prognosis and treatment regimen for IDC and ILC. Researchers should further study the ER negative/PR negative population to identify treatment and prognostic models that will facilitate the development of individualized therapy for these patients, which is needed for good outcomes.

The Real-world Outcomes of Patients With Advanced Invasive Lobular Carcinoma of the Breast Compared With Invasive Ductal Carcinoma: A Review at a Single Institution.

BACKGROUND: The real-world outcomes of patients with advanced invasive lobular carcinoma (ILC) of the breast are unclear because of its rarity. PATIENTS AND METHODS: We identified 435 patients with estrogen receptor-positive (ER+), HER2-negative (HER2-) advanced breast cancer treated at our Institute between 2002 and 2019, and analyzed their outcomes retrospectively. RESULTS: We identified 29 patients with advanced ILC. At presentation, they had a lower rate of lung metastasis (p=0.0053) but a higher rate of stomach metastasis (p=0.0379) compared with other patients with advanced breast cancer. Median overall survival did not differ; however, multivariate analyses showed that ILC histopathology was a risk factor for poorer overall survival (hazard ratio=3.43, p=0.0038) in patients with de novo stage IV ER+ HER2- breast cancer. Patients with ILC showed a markedly different patten of subsequent metastasis, such as less in the lung and more in the stomach, leptomeninges, and bone marrow. CONCLUSION: According to our retrospective study, in patients with de novo stage IV ER+ HER2- breast cancer, ILC histopathology was associated with increased risk of death.

Nomograms predict survival of patients with lymph node-positive, luminal a breast cancer.

BACKGROUND: To develop nomograms for the prediction of the 1-, 3-, and 5-year overall survival (OS) and breast cancer-specific survival (BCSS) for patients with lymph node positive, luminal A breast cancer. METHODS: Thirty-nine thousand fifty-one patients from The Surveillance, Epidemiology, and End Results (SEER) database were included in our study and were set into a training group (n = 19,526) and a validation group (n = 19,525). Univariate analysis and Cox proportional hazards analysis were used to select variables and set up nomogram models on the basis of the training group. Kaplan-Meier curves and the log-rank test were adopted in the survival analysis and curves plotting. C-index, calibration plots and ROC curves were used to performed internal and external validation on the training group and validation group. RESULTS: Following independent factors were included in our nomograms: Age, marital status, grade, ethnic group, T stage, positive lymph nodes numbers, Metastasis, surgery, radiotherapy, chemotherapy. In both the training group and testing group, the calibration plots show that the actual and nomogram-predicted survival probabilities are consistent greatly. The C-index values of the nomograms in the training and validation cohorts were 0.782 and 0.806 for OS and 0.783 and 0.804 for BCSS, respectively. The ROC curves show that our nomograms have good discrimination. CONCLUSIONS: The nomograms may assist clinicians predict the 1-, 3-, and 5-year OS and BCSS of patients with lymph node positive, luminal A breast cancer.

Phase III randomised trial comparing intense dose-dense chemotherapy to tailored dose-dense chemotherapy in high-risk early breast cancer (GAIN-2).

BACKGROUND: The GAIN-2 trial was designed to identify a superior intense dose-dense (idd) strategy for high-risk patients with early breast cancer. Here, we report an interim analysis, at which the predefined futility boundary was crossed. PATIENTS AND METHODS: GAIN-2 was an open-label, randomised, multicentre phase III trial. Two thousand eight hundred and eighty seven patients were randomised 1:1 between three courses each of idd epirubicin (E) 150 mg/m2, nab-paclitaxel (nP) 330 mg/m2 and cyclophosphamide (C) 2000 mg/m2 (iddEnPC) versus four cycles of leucocyte nadir-based tailored and dose-dense EC (dtEC) followed by four cycles of tailored and dose-dense docetaxel (dtD) (dtEC-dtD). RESULTS: The duration of median follow-up was 45.8 (range 0.0-88.3) months. Trial objectives included invasive disease-free survival (iDFS) as the primary end-point. A total of 593 patients received the treatment as neoadjuvant chemotherapy. At the time of futility interim analysis, 414 events for iDFS were reported. Overall, there was no difference in iDFS between iddEnPC and dtEC-dtD with 4-year iDFS rates of 84.3% (95% confidence interval (CI) 82.0-86.4%). Among all predefined subgroups, hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR+/HER2-), lobular cancer and ≤50 years subgroups predicted for better iDFS in the dtEC-dtD arm. Overall, 88.1% of patients completed all treatment in both arms. Haematological toxicity grade 3/4 and grade 3/4 non-haematological adverse events were significantly higher with iddEnPC (iddEnPC 50.8% vs dtEC-dtD 45.1%, P = 0.002), especially arthralgia and peripheral sensory neuropathy. Two treatment-related deaths occurred during dtEC-dtD, corresponding to a low mortality rate of 0.07%. CONCLUSIONS: iDFS is equal in both regimens, but tailoring dose-dense chemotherapy improved outcomes in HR+/HER2-, lobular cancer and patients ≤50 years.

Long-term prognosis in breast cancer is associated with residual disease after neoadjuvant systemic therapy but not with initial nodal status.

BACKGROUND: This follow-up analysis of a Swedish prospective multicentre trial had the primary aim to determine invasive disease-free (IDFS), breast cancer-specific (BCSS) and overall survival (OS) rates, and their association with axillary staging results before and after neoadjuvant systemic therapy for breast cancer. METHODS: Women who underwent neoadjuvant systemic therapy for clinically node-positive (cN+) or -negative (cN0) primary breast cancer between 2010 and 2015 were included. Patients had a sentinel lymph node biopsy before and/or after neoadjuvant systemic therapy, and all underwent completion axillary lymph node dissection. Follow-up was until February 2019. The main outcome measures were IDFS, BCSS and OS. Univariable and multivariable Cox regression analyses were used to identify independent factors associated with survival. RESULTS: The study included a total of 417 women. Median follow-up was 48 (range 7-114) months. Nodal status after neoadjuvant systemic therapy, but not before, was significantly associated with crude survival: residual nodal disease (ypN+) resulted in a significantly shorter 5-year OS compared with a complete nodal response (ypN0) (83·3 versus 91·0 per cent; P = 0·017). The agreement between breast (ypT) and nodal (ypN) status after neoadjuvant systemic therapy was high, and more so in patients with cN0 tumours (64 of 66, 97 per cent) than those with cN+ disease (49 of 60, 82 per cent) (P = 0·005). In multivariable analysis, ypN0 (hazard ratio 0·41, 95 per cent c.i. 0·22 to 0·74; P = 0·003) and local radiotherapy (hazard ratio 0·23, 0·08 to 0·64; P = 0·005) were associated with improved IDFS, and triple-negative molecular subtype with worse IDFS. CONCLUSION: The present findings underline the prognostic significance of nodal status after neoadjuvant systemic therapy. This confirms the clinical value of surgical axillary staging after neoadjuvant systemic therapy.

Association of antidiabetic medication and statins with survival from ductal and lobular breast carcinoma in women with type 2 diabetes.

We investigated the survival of female patients with pre-existing type 2 diabetes (T2D) diagnosed with invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) of breast, in relation to the use of metformin, other antidiabetic medication (ADM) and statins. The study cohort consisted of 3,165 women (2,604 with IDC and 561 with ILC). The cumulative mortality from breast cancer (BC) and from other causes was calculated using the Aalen-Johansen estimator. The cause-specific mortality rates were analysed by Cox models, and adjusted hazard ratios (HRs) were estimated for the use of different medications. No evidence of an association of metformin use with BC mortality was observed in either IDC (HR 0.92, 95% confidence interval [CI] 0.64-1.31) or ILC (HR 0.68, 95% CI 0.32-1.46) patients, when compared to other oral ADMs. The mortality from other causes was found to be lower amongst the IDC patients using metformin (HR 0.64, 95% CI 0.45-0.89), but amongst ILC patients the evidence was inconclusive (HR 1.22, 95% CI 0.64-2.32). Statin use was consistently associated with reduced mortality from BC in IDC patients (HR 0.77, 95% CI 0.62-0.96) and ILC patients (HR 0.59, 95% CI 0.37-0.96), and also mortality from other causes in IDC patients (HR 0.81, 95% CI 0.67-0.96) and in ILC patients (HR 0.66, 95% CI 0.43-1.01). We found no sufficient evidence for the possible effects of metformin and statins on the prognosis of BC being different in the two histological subtypes.

Competing-Risk Nomograms for Predicting the Prognosis of Patients With Infiltrating Lobular Carcinoma of the Breast.

BACKGROUND: Infiltrating lobular carcinoma (ILC) is the second most common histologic subtype of breast cancer. We assessed the rates of cause-specific death in ILC patients with the aim of establishing competing-risk nomograms for predicting their prognosis. PATIENTS AND METHODS: Data on ILC patients were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. The cumulative incidence function was used to calculate the cumulative incidence rates of cause-specific death, and Gray's test was applied to test the differences in cumulative incidence rates among groups. We then identified independent prognostic factors by applying the Fine-Gray proportional subdistribution hazard analysis method and established nomograms based on the results. Calibration curves and the concordance index were employed to validate the nomograms. RESULTS: The study enrolled 11,361 patients. The 3-, 5-, and 10-year overall cumulative incidence rates for those who died of ILC were 3.1%, 6.2%, and 12.2%, respectively, whereas the rates for those who died from other causes were 3.2%, 5.8%, and 14.1%. Age, marriage, grade, size, regional node positivity, American Joint Committee on Cancer M stage, progesterone receptor, and surgery were independent prognostic factors for dying of ILC, whereas the independent prognostic factors for dying of other causes were age, race, marriage, size, radiation, and chemotherapy. The nomograms were well calibrated and had good discrimination ability. CONCLUSION: We applied competing-risk analysis to ILC patients based on the SEER database and established nomograms that perform well in predicting the cause-specific death rates at 3, 5, and 10 years after the diagnosis.

Prognostic Factors and Survival Outcomes among Patients with Breast Cancer and Brain Metastases at Diagnosis: A National Cancer Database Analysis.

INTRODUCTION: The aim of this study was to assess for clinicopathologic and socioeconomic features that predict improved survival for patients with advanced breast cancer with synchronous brain metastases at diagnosis. METHODS: We utilized the National Cancer Database (NCDB) to identify all patients with brain metastases present at diagnosis, with adequate information on receptor status (ER, PR, Her2), clinical T stage of cT1-4, clinical M1, with 3,943 patients available for analysis. The association between brain metastases patterns and patient/disease variables was examined by robust Poisson regression model. Cox proportional hazards model was used to quantify the associations between overall survival (OS) and these variables. RESULTS: In univariable analysis, OS was significantly associated with the number of sites of metastases (p < 0.0001). Patients with 2 or more additional extracranial sites of metastases had significantly worse OS (median 8.8 months, 95% confidence interval [CI] 7.8, 9.9) than patients with brain metastases only (median OS 10.6 months, 95% CI 9.4, 12.9) or brain metastases plus one other extracranial site of metastases (median OS 13.1 months, 95% CI 11.8, 14.4). Risk factors which predicted poor prognosis included triple-negative disease, high comorbidity score, poorly differentiated tumors, invasive lobular histology, multi-organ involvement of metastases, and government or lack of insurance. Factors which improve survival include younger age and Hispanic race. DISCUSSION/CONCLUSION: Using a large NCDB, we identified various factors associated with prognosis for patients with brain metastases at the time of breast cancer diagnosis. Insurance status and related socioeconomic challenges provide potential areas for improvement in care for these patients. This information may help stratify patients into prognostic categories at the time of diagnosis to improve treatment plans.

Invasive lobular carcinoma of the breast: the increasing importance of this special subtype.

Invasive lobular carcinoma (ILC) is the most common of the breast cancer special types, accounting for up to 15% of all breast cancer cases. ILCs are noted for their lack of E-cadherin function, which underpins their characteristic discohesive growth pattern, with cells arranged in single file and dispersed throughout the stroma. Typically, tumours are luminal in molecular subtype, being oestrogen and progesterone receptor positive, and HER2 negative. Since last reviewing the lobular literature (McCart Reed et al., Breast Cancer Res 17:12, 2015), there has been a considerable increase in research output focused on this tumour type, including studies into the pathology and management of disease, a high-resolution definition of the genomic landscape of tumours as well as the evolution of several potential therapeutic avenues. There abounds a huge amount of new data, which we will review herein.

Ovarian metastases from breast cancer: A report of 24 cases.

OBJECTIVE: The purpose of this study was to investigate the epidemiological, demographical characteristics and survival outcomes of the patients with ovarian metastases from breast cancer. STUDY DESIGN: Medical records of 24 patients with pathologically confirmed metastases in ovaries treated at two tertiary hospitals between 2000 and 2019 were reviewed retrospectively. Patients' as well as tumor characteristics, and treatment data were collected. Ovarian metastases of breast cancer were documented using a system of analogous to the FIGO classification for ovarian cancer. Survival after primary breast cancer diagnosis and after diagnosis of metastases in ovaries were calculated. Outcomes were compared between the three different procedures bilateral salpingo-oophorectomy, total hysterectomy with bilateral salpingo-oophorectomy, and total hysterectomy with bilateral salpingo-oophorectomy with omentectomy. RESULTS: The majority of patients had estrogen receptor positive (87 %) and progesterone receptor positive (91 %), 80 % patients were HER2/neu negative. The majority of patients had primary tumor stage by TNM classification T1 (33 %) and T2 (50 %); node- negative (25 %) and node-positive (75 %); 71 % of patients had no distal metastases in primary breast cancer diagnosis (M0) while 29 % of patients had distant metastases. The median age of primary breast cancer diagnosis was 46.5 ± 10.4 years (range 25-69). The mean time to occurrence of secondary ovarian malignancies after primary breast cancer diagnosis was 62.9 ± 62.8 months (range 0-219). The majority of women underwent adnexectomy (37.5 %) or total hysterectomy with adnexectomy (37.5 %). The mean survival after breast cancer treatment was 72 months, and the mean survival after discovery of ovarian metastases was 25 months. CONCLUSIONS: Our results showed that more radical surgical treatment of metastases to ovaries has no increase of survival among patients. However, it should be noted that this may be affected by different stage of primary disease. Thus, larger and more standardized studies need to be done in order to confirm prognostic features and the choice of surgical volume.

The correlation of 18F-FDG PET/CT metabolic parameters, clinicopathological factors, and prognosis in breast cancer.

PURPOSE: To study the imaging parameters of 18F-fluorodeoxy glucose (18F-FDG) in breast cancer on positron emission tomography/computed tomography (PET/CT)-the correlation of clinical pathological factors and prognosis among the maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of lesions for patients. METHODS: From January 2012 to December 2014, a total of 125 female patients were treated in our hospital for the first time and were diagnosed as breast cancer by histopathology. They were selected as the research subjects. All of them had complete 18F-FDG PET/CT examination data before surgery, the postoperative clinicopathological information, and follow-up data. They were divided into the event group (38 cases) and the event-free group (87 cases) according to whether local recurrence or distant metastasis occurred after the follow-up, with the follow-up time 4-60 months. The correlation on 18F-FDG PET/CT metabolic parameters of breast cancer with clinicopathological factors and prognosis was retrospectively evaluated. RESULTS: The primary lesions of 125 cases with breast cancers all had higher 18F-FDG uptake, and the SUVmax, MTV, and TLG of the primary tumors in the event group were significantly higher than those in the event-free group (t = 2.645, 2.782, 15.263, p = 0.011, 0.008, 0.000), p < 0.05; SUVmax, MTV, and TLG of primary breast cancer have no correlation with age and tumor site of patient (p > 0.05); there were statistically significant differences in the SUVmax, MTV, and TLG of primary tumor in the comparison of different tumor size, T stage, N stage, and histological grades (p < 0.05); all of SUVmax, MTV, and TLG in the estrogen receptor (ER) and/or progesterone receptor (PR) positive groups were lower than those in the negative group, with statistically significant difference (p < 0.05); the SUVmax, MTV, and TLG of human epidermal growth factor receptor 2 (HER2) positive group, proliferating cell nuclear antigen (Ki-67) high expression group were higher than those in the negative group and low expression group, with statistically significant difference (p < 0.05). There were 38 recurrence and metastasis cases within 125 cases with breast cancer in 5 years after operation, with the total recurrence and metastasis rate as 30.40% (38/125). The event-free survival rate in the SUVmax ≥ 8.64 group was significantly lower than that in the SUVmax < 8.64 group (p < 0.01). CONCLUSIONS: The metabolic parameters of 18F-FDG PET/CT in breast cancer can reflect the biological behavior of the tumor indirectly; therefore, it was studied on the related correlation to provide the guidance of clinical individualized comprehensive treatment and prognostic judgment.

The prognosis of invasive ductal carcinoma, lobular carcinoma and mixed ductal and lobular carcinoma according to molecular subtypes of the breast.

BACKGROUND: To investigate the prognosis of females with invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), and mixed invasive ductal and lobular carcinoma (IDLC) according to hormone receptor (HR) and HER2 status. METHODS: Data of 171,881 patients from the SEER database were analyzed. Propensity score matching was used to balance the covariates. Breast cancer-specific survival (BCSS) and overall survival (OS) of IDC, ILC, and IDLC were investigated. RESULTS: Patients with ILC were older, had lower tumor grade, higher tumor stage, larger tumor size, more nodal metastasis, higher estrogen receptor(+), lower HER2(-), and less likely to receive partial mastectomy and chemotherapy compared with IDC and IDLC. ILC and IDLC showed better prognosis than IDC after matching by Kaplan-Meier curves. Multivariate Cox regression showed better OS of ILC and IDLC compared with IDC with hazard ratio and a 95% confidence interval of 0.84 (0.77-0.90) and 0.91 (0.83-1.00), respectively. For HR(+)HER2(-) subgroup, ILC showed better OS than IDC; IDC showed worse BCSS and OS than IDLC. For HR(+)HER2(+); ILC showed better OS compared with IDLC; there were no survival differences of IDC, ILC, and IDLC for HER2(+). For HR(-)HER2(-), ILC and IDC showed better BCSS and OS compared with IDLC by multivariate analysis. CONCLUSIONS: The prognoses of female patients with IDC, ILC or IDLC were associated with the molecular subtypes of breast carcinoma. Management decisions should be based on pathological types and molecular subtypes.

Prognostic factors and survival according to tumour subtype in women presenting with breast cancer bone metastases at initial diagnosis: a SEER-based study.

BACKGROUND: Tumour subtype has a significant effect on bone metastasis in breast cancer, but population-based estimates of the prognosis of patients with bone metastases at breast cancer diagnosis are lacking. The aim of this study was to analyse the influence of tumour subtype and other factors on the prognosis and survival of patients with bone metastases of breast cancer. METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) Program data from 2012 to 2016, a retrospective cohort study was conducted to investigate stage IV breast cancer patients with bone metastases. Stage IV patient characteristics according to subtype were compared using chi-square tests. Overall survival (OS) and prognostic factors were compared using the Kaplan-Meier method and the Cox proportional hazards model, respectively. RESULTS: A total of 3384 stage IV patients were included in this study; 63.42% were HR+/HER2-, 19.86% were HR+/HER2+, 9.34% were HR-/HER2-, and 7.39% were HR-/HER2+. The median OS for the whole population was 38 months, and 33.9% of the patients were alive at 5 years. The median OS and five-year survival rate were significantly different among stage IV breast cancer patients with different molecular subtypes (p < 0.05). Multivariate Cox regression analysis showed that age of 55-59 (HR = 1.270), black race (HR = 1.317), grade III or IV (HR = 1.960), HR-/HER2- (HR = 2.808), lung metastases (HR = 1.378), liver metastases (HR = 2.085), and brain metastases (HR = 1.903) were independent risk factors for prognosis; married status (HR = 0.819), HR+/HER2+ (HR = 0.631), HR-/HER2+ (HR = 0.716), insurance (HR = 0.587) and surgery (HR = 0.504) were independent protection factors of prognosis. There was an interaction between the HR+/HER2+ subtype and other metastases (except bone metastases, HR = 0.694, 95% CI: 0.485-0.992), but the interaction between race and subtype did not reach significance for prognosis. CONCLUSIONS: There were substantial differences in OS according to tumour subtype. In addition to tumour subtype, other independent predictors of OS were age at diagnosis, race, marital status, insurance, grade, surgery and visceral metastases. There was an interaction between the HR+/HER2+ subtype and other metastases (except bone metastases) for prognosis. Tumour subtype, as a significant prognostic factor, warrants further investigation.

The effect of postmastectomy radiotherapy in node-positive triple-negative breast cancer.

BACKGROUND: The value of postmastectomy radiotherapy (PMRT) for pathological node-positive triple-negative breast cancers (TNBC) remains debatable. The aim of this population-based retrospective study was to evaluate the effect of PMRT on survival outcomes in this population. METHODS: Patients diagnosed with stage T1-4N1-N3M0 TNBC between 2010 and 2014 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. We used univariate and multivariate Cox regression hazards method to determine the independent prognostic factors associated with 3-year breast cancer-specific survival (BCSS). The effect of PMRT on 3-year BCSS was analyzed after stratification by pathological staging of groups. RESULTS: Of the 4398 patients included in this study, 2649 (60.2%) received PMRT. Younger age, black ethnicity, and advanced tumor (T) and nodal (N) stage were the independent predictors associated with PMRT receipt (all P < 0.05). Patients who received PMRT showed better 3-year BCSS (OR = 0.720, 95% CI = 0.642-0.808, P < 0.001) than those that did not. The effect of PMRT on 3-year BCSS was analyzed after stratification by pathological staging of groups. The results showed that PMRT was associated with better 3-year BCSS in patients with stage T3-4N1 (P = 0.042), T1-4N2 (P < 0.001), and T1-4N3 (P < 0.001), while comparable 3-year BCSS was found between the PMRT and non-PMRT cohorts with T1-2N1 disease (P = 0.191). CONCLUSIONS: Radiotherapy achieved better 3-year BCSS in TNBC patients with stage T3-4N1 and T1-4N2-3 disease. However, no survival benefit was found with the addition of PMRT in patients with T1-2N1 TNBC.

Long-term Oncologic Outcomes of Immediate Breast Reconstruction vs Conventional Mastectomy Alone for Breast Cancer in the Setting of Neoadjuvant Chemotherapy.

Importance: An increasing number of patients with breast cancer receiving neoadjuvant chemotherapy (NACT) undergo immediate breast reconstruction (IBR) with nipple-sparing mastectomy (NSM) or skin-sparing mastectomy (SSM) as surgical treatment. However, the oncologic efficacy and safety of this treatment sequencing strategy is unclear. Objective: To compare the long-term oncologic outcomes of IBR with NSM/SSM and conventional mastectomy (CM) alone for breast cancer in the NACT setting. Design, Setting, and Participants: A retrospective, propensity score-matched case-control study was conducted at Asan Medical Center, Seoul, Korea. A total of 1266 patients with breast cancer who underwent NACT followed by mastectomy with or without breast reconstruction between January 1, 2010, and November 30, 2016, were included. Data analysis was performed from July 1, 2019, to January 24, 2020. After propensity score matching, 323 patients who underwent IBR with NSM/SSM and 323 who underwent CM alone were selected for comparison of long-term oncologic outcomes. Main Outcomes and Measures: The 5-year local recurrence-free survival, disease-free survival, distant metastasis-free survival, and overall survival rates were calculated using the Kaplan-Meier method and compared using log-rank tests. Hazard ratios (HRs) and 95% CIs were estimated using the Cox proportional hazards regression model. Results: After matching, the median follow-up periods were 67 (range, 17-125) months for the IBR group and 68 (range, 17-126) months for the CM-alone group. Median age of the women in the IBR group was 42 (range, 23-72) years; median age of those in the CM-alone group was 46 (range, 30-75) years. No significant differences were observed between the IBR and CM-alone groups in local recurrence (3.7% vs 3.4%; P = .83), regional recurrence (7.1% vs 5.3%; P = .33), or distant metastasis (17.3% vs 18.6%; P = .68) rates. There was also no significant difference between the IBR and CM-alone groups in 5-year local recurrence-free survival (95.6% vs 96.7%; HR, 1.124; 95% CI, 0.495-2.549; P = .78), disease-free survival (76.5% vs 79.9%; HR, 1.089; 95% CI, 0.790-1.500; P = .60), distant metastasis-free survival (82.5% vs 82.5%; HR, 0.941; 95% CI, 0.654-1.355; P = .74), or overall survival (92.0% vs 89.3%; HR, 0.847; 95% CI, 0.530-1.353; P = .49) rates. Conclusions and Relevance: The long-term oncologic outcomes of IBR with NSM/SSM for breast cancer in this study appeared to be comparable to those of CM alone after NACT, suggesting the feasibility of IBR with NSM/SSM in the NACT setting.

A nomogram for determining the disease-specific survival in invasive lobular carcinoma of the breast: A population study.

We aimed to establish and validate a nomogram for predicting the disease-specific survival of invasive lobular carcinoma (ILC) patients.The Surveillance, Epidemiology, and End Results program database was used to identify ILC from 2010 to 2015, in which the data was extracted from 18 registries in the US. Multivariate Cox regression analysis was performed to identify independent prognostic factors and a nomogram was constructed to predict the 3-year and 5-year survival rates of ILC patients based on Cox regression. Predictive values were compared between the new model and the American Joint Committee on Cancer staging system using the concordance index, calibration plots, integrated discrimination improvement, net reclassification improvement, and decision-curve analyses.In total, 4155 patients were identified. After multivariate Cox regression analysis, nomogram was established based on a new model containing the predictive variables of age, the primary tumor site, histology grade, American Joint Committee on Cancer TNM (tumor node metastasis) stages II, III, and IV, breast cancer subtype, therapy modality (surgery and chemotherapy). The concordance index for the training and validation cohorts were higher for the new model (0.781 and 0.832, respectively) than for the old model (0.733 and 0.779). The new model had good performance in the calibration plots. Net reclassification improvement and integrated discrimination improvement were also improved. Finally, decision-curve analyses demonstrated that the nomogram was clinically useful.We have developed a reliable nomogram for determining the prognosis and treatment outcomes of ILC. The new model facilitates the choosing of superior medical examinations and the optimizing of therapeutic regimens with cooperation among oncologists.

MRI background parenchymal enhancement, fibroglandular tissue, and mammographic breast density in patients with invasive lobular breast cancer on adjuvant endocrine hormonal treatment: associations with survival.

BACKGROUND: To investigate if baseline and/or changes in contralateral background parenchymal enhancement (BPE) and fibroglandular tissue (FGT) measured on magnetic resonance imaging (MRI) and mammographic breast density (MD) can be used as imaging biomarkers for overall and recurrence-free survival in patients with invasive lobular carcinomas (ILCs) undergoing adjuvant endocrine treatment. METHODS: Women who fulfilled the following inclusion criteria were included in this retrospective HIPAA-compliant IRB-approved study: unilateral ILC, pre-treatment breast MRI and/or mammography from 2000 to 2010, adjuvant endocrine treatment, follow-up MRI, and/or mammography 1-2 years after treatment onset. BPE, FGT, and mammographic MD of the contralateral breast were independently graded by four dedicated breast radiologists according to BI-RADS. Associations between the baseline levels and change in levels of BPE, FGT, and MD with overall survival and recurrence-free survival were assessed using Kaplan-Meier survival curves and Cox regression analysis. RESULTS: Two hundred ninety-eight patients (average age = 54.1 years, range = 31-79) fulfilled the inclusion criteria. The average follow-up duration was 11.8 years (range = 2-19). Baseline and change in levels of BPE, FGT, and MD were not significantly associated with recurrence-free or overall survival. Recurrence-free and overall survival were affected by histological subtype (p < 0.0001), number of metastatic axillary lymph nodes (p < 0.0001), age (p = 0.01), and adjuvant endocrine treatment duration (p < 0.001). CONCLUSIONS: Qualitative evaluation of BPE, FGT, and mammographic MD changes cannot predict which patients are more likely to benefit from adjuvant endocrine treatment.

Case report: 5-year progression free survival and complete liver response in a patient with metastatic breast cancer treated with everolimus plus exemestane.

RATIONALE: Within a rapidly expanding therapeutic armamentarium, the combination of everolimus (Eve) plus exemestane (Exe) utility needs to be reinstated in hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) metastatic breast cancer (MBC). PATIENT CONCERNS: We herein report on a patient affected by HR+ HER2- MBC treated with radical surgery after neoadjuvant chemotherapy, who relapsed early on adjuvant tamoxifen, progressed rapidly on first line anastrozole, and failed treatment with third line capecitabine. DIAGNOSES: Metastatic luminal breast cancer progressed under standard endocrine therapy and chemotherapy. INTERVENTIONS: Third line with Eve plus Exe was given after chemotherapy. OUTCOMES: Patient experienced a 5-year progression free interval. LESSONS: Eve plus Exe remains a valid option in HR+HER2- MBC.

A comparison between young and old patients with triple-negative breast cancer: biology, survival and metastatic patterns.

PURPOSE: To determine the biology, recurrence rate, metastatic patterns and survival times in primary triple-negative breast cancer (TNBC) with focus on the comparison between younger and elderly patients. METHODS: Patients with primary TNBC stage I-IV diagnosed from 2007 to 2015 were identified and information on tumor biology, stage, treatment, recurrences and death recorded. RESULTS: A total of 524 patients, median age 60 years (range 24-94) with a median follow-up of 55 months (range 0-129) were identified. Stage was similar in younger (< 40 years) (n = 58) and older (> 74 years) (n = 96) patients (p = 0.37). A statistically significant difference was found concerning histopathologic grade (p = 0.006) and Ki67 (median 80% versus 70%; p = 0.002) but not for LVI (p = 0.9) with more aggressive tumors among younger patients. Adjuvant/neoadjuvant chemotherapy was more frequently given to younger compared with older patients (96% versus 12%; p = 0.0005). Only brain (p = 0.016) and liver (p = 0.047) metastases were more often registered among younger patients while other locations were similar. Shorter survival times, recurrence-free survival (RFS), distant disease-free survival (DDFS) and breast cancer-specific survival (BCSS) were found in the older group, although not after adjusting for adjuvant/neoadjuvant chemotherapy. Most deaths (68%) in the older group were caused by TNBC. When comparing patients > 75 years (n = 92) with ≤ 75 years (n = 432), a worse outcome among older was also observed: RFS (p = 0.00012), DDFS (p = 0.00041), BCSS (p < 0.0001) and survival following distant metastasis (p = 0.0064) CONCLUSIONS: Primary TNBC in younger patients is more often of poor differentiation grade and highly proliferative compared with older patients. The majority of older patients still have grade III tumors with a Ki67 > 60% and outcome is poor. Few older patients in our study were treated with chemotherapy both in adjuvant and palliative setting, underlining the need for more prospective trials and treatment options suitable for this patient population.