Effect of Neoadjuvant Concurrent Chemoradiation on Operability and Survival in Locally Advanced Inoperable Breast Cancer.

PURPOSE: Inoperable locally advanced breast cancers (LABCs) are treated with neoadjuvant chemotherapy. We studied the use of neoadjuvant concurrent chemoradiation (NACCRT) in patients with inoperable LABC. METHODS AND MATERIALS: From May 2017 to December 2021, the study recruited patients with stage III inoperable LABC. Treatment included 4 cycles of doxorubicin and cyclophosphamide and 4 cycles of paclitaxel, along with concurrent radiation therapy to a total dose of 46 Gy. Thereafter, all patients were evaluated for surgery, and additional treatments were given based on receptor status. The effects of NACCRT on pathologic complete response (pCR), operability, and survival were analyzed. RESULTS: The study involved 202 female patients with a median age of 52 years. Of these, 23.7% had IIIA, 65.3% had IIIB, and 10.8% had IIIC disease. Hormone receptor-positive disease was observed in 44.6% of patients, triple-negative breast cancer was observed in 24.8% of patients, and Human epidermal growth factor receptor 2 (HER2)-positive disease was observed in 30.7% of patients. Modified radical mastectomy (MRM) was performed in 88.1% of patients, 8.5% of patients remained inoperable, and 3.4% of patients declined surgery. Among the patients who underwent MRM, 36.5% of patients had a pCR. Patients who were operable and underwent MRM had complete resections and had negative margins. pCR was observed in 16% with hormone receptor-positive disease, in 45.6% with triple-negative breast cancer, and in 60.7% with HER2-positive disease. Grade 3 skin reactions were observed in 19.3% of patients. Postoperative wound morbidity requiring hospitalization was observed in 10.6% of patients. After a median follow-up of 42 months, the 4-year event-free survival and overall survival rates were 63.4% and 71.5%, respectively. HER2-positive patients who achieved a pCR had significantly improved event-free survival and overall survival. CONCLUSIONS: Our study shows that using NACCRT can improve operability and survival outcomes in patients with inoperable LABC.

Real-World Experience of Treating Young Adult Patients with Breast Cancer from a Single Center in Southern India.

Priya IyerBackground Breast cancer in young adults is rare and accounts for 5 to 6% of all cancers in this age group. We conducted the present study to look at the demographic features, clinical presentation, and outcomes in this group of patients treated at our center. Patients and Methods The study included breast cancer patients between the age of 15 and 30 years treated at our institute from January 2009 to December 2016. Data were analyzed retrospectively from case records. Event-free survival (EFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Results Young adult breast cancers were reported in 145 out of 6,000 patients (2.41%) diagnosed with breast cancer in the study period. The median age of the patients was 29 years (range: 21-30 years). Stage I, II, III, and IV was observed in 3.4, 33.7, 46.2, and 16.5% of patients, respectively. The median follow-up was 45 months (range: 1.7-128.1 months). The 5-year EFS and OS for stage I, II, III, and IV was 100, 74.5, 47.9, and 0% and 100, 90.8, 55.1, and 0%, respectively. On univariate analysis, stage of the disease and pregnancy-associated breast cancers were found to have a significant association with decreased EFS and OS ( p < 0.001, p = 0.008 and p < 0.001, p = 0.001, respectively). On multivariate analysis, stage of disease and pregnancy-associated breast cancers remained significant predictors of EFS and OS. Conclusion Breast cancers in young adults are rare but need to be diagnosed at an early stage to improve survival. Pregnancy-associated breast cancers need to be managed optimally without delay owing to their aggressive tumor biology.

Metaplastic carcinoma of the breast: real-world outcome from a tertiary cancer centre in India.

Metaplastic carcinoma (MPC) is a rare subgroup of breast tumours accounting for <5% of all invasive breast cancers. Histologically confirmed 40 MPC from January 2001 to December 2018 were identified from our electronic database: stage I 2.5% (n = 1), stage II 40% (n = 16), stage III 45% (n = 18) and stage IV 12.5% (n = 5). The mean tumour size was 6 cm, node-negative in 60%, and hormone receptor-negative in 75%. Among the 35 non-metastatic patients, 17 (48.6%) received initial neoadjuvant treatment (NAT), followed by surgery, and only 1 had a complete pathological response. At a median follow-up of 60 months, 17% (n = 6) had a recurrence. All six of them had lung metastasis. The 5-year overall survival (OS) and disease-free survival were 64.4% and 66.3%, respectively. Age more than 46 years (p = 0.027), tumour size more than 5 cm (p = 0.037), and nodal positivity (p = 0.001) were predictors of OS. In node-positive patients, the 5-year OS in those who underwent initial surgery was 80% and after NAT was 21.4% (p = 0.069). In node-negative patients, the 5-year OS after initial surgery was 83.3% and after NAT was 90% (p = 0.380). A statistical significance could not be demonstrated due to the small number of patients. Due to chemoresistance, the concept of initial NAT in MPC of the breast is a subject to be studied in the future. Upfront surgery should be considered for operable diseases (including stage III), followed by a decision on adjuvant therapy. Optimal treatment and effective systemic therapy regimens are yet to be defined.

Forecasting factors and outcomes in hawkish inflammatory breast carcinoma - A single center data exploration.

INTRODUCTION: Inflammatory breast carcinoma (IBC) is an aggressive clinical syndrome of invasive breast carcinoma. There is paucity of data regarding the outcomes in IBC. OBJECTIVES: Analyses of OS and Event-free survival (EFS) in nonmetastatic and metastatic IBC and to find prognostic factors influencing them. METHODOLOGY: In this single center, retrospective study the data of patients fulfilling the clinical criteria of IBC were retrieved from 2016 to 2021. The impact of prognostic factors on OS and EFS were analysed by log rank test (univariate analysis). The OS and EFS were depicted as Kaplan Meier survival curves. RESULTS: There were 22 patients with IBC. Median follow-up was 17 months. The median OS was significantly better in non-metastatic(M0) compared to metastatic IBC (25 months vs 6 months) with 3year OS rate of 50% vs 0% respectively. The post-menopausal status, grade 2 histology and trimodality treatment showed better outcome while N3 stage at diagnosis had worse outcome in M0 group. The lesser HR expression, lesser pCR rates, higher N3 proportion, liver metastasis and multiple metastatic site involvement contributed to the worse outcome observed in this study. CONCLUSION: The aggressive clinicopathological features of IBC in the present study resulted in less favourable outcome compared to literature review. Improved outcome with trimodality highlights the emergent need for additional targeted therapy to improve pCR and operability.

The continuing conundrum in oligometastatic breast carcinoma: A real-world data.

The optimal management in Oligometastatic (OM) breast carcinoma is not defined. OBJECTIVES: To identify the prognostic factors influencing OM and the effect of Locoregional treatment (LRT) on survival in OM. METHODOLOGY: Patients with ≤5 metastases and each with ≤ 5 cm size were defined as OM. Data of OM were extracted from the Institute Registry between 2012 and 2018. The impact of prognostic factors on survival was analysed by univariate and multivariate Cox regression. The Kaplan Meier survival curves were used to plot PFS and OS. RESULTS: There were 170 patients with OM. The median follow-up was 61 months. Median OS was 43.3 months. The median OS was 74 months in OMD vs 22.7 months in Oligorecurrent disease (ORD) with 5year OS rate of 55.3% vs 16.5% respectively. In the multivariate analyses of OMD both Ki67 ≤ 50% and hormone therapy (HT) showed significant favourable survival outcome. While premenopausal status and HT showed significant survival benefits in ORD. The worse survival outcome in ORD could be because of their aggressive biology and deficit in LRT compared to literature review. The prognostic factors were swayed by the uneven distribution of HR status, grade and Ki67. CONCLUSION: The survival of OM was influenced by OMD, Ki67 ≤ 50%, premenopausal status and HT. The lesser survival rates of OM in the long term suggest the need for curative LRT to metastatic sites and primary tumor. The potential role of HT and targeted therapy with or without LRT need to be assessed in future randomised trials.

Dietary fibre to reduce colon cancer risk in Alaska Native people: the Alaska FIRST randomised clinical trial protocol.

INTRODUCTION: Diet, shown to impact colorectal cancer (CRC) risk, is a modifiable environmental factor. Fibre foods fermented by gut microbiota produce metabolites that not only provide food for the colonic epithelium but also exert regulatory effects on colonic mucosal inflammation and proliferation. We describe methods used in a double-blinded, randomised, controlled trial with Alaska Native (AN) people to determine if dietary fibre supplementation can substantially reduce CRC risk among people with the highest reported CRC incidence worldwide. METHODS AND ANALYSES: Eligible patients undergoing routine screening colonoscopy consent to baseline assessments and specimen/data collection (blood, urine, stool, saliva, breath and colon mucosal biopsies) at the time of colonoscopy. Following an 8-week stabilisation period to re-establish normal gut microbiota post colonoscopy, study personnel randomise participants to either a high fibre supplement (resistant starch, n=30) or placebo (digestible starch, n=30) condition, repeating stool sample collection. During the 28-day supplement trial, each participant consumes their usual diet plus their supplement under direct observation. On day 29, participants undergo a flexible sigmoidoscopy to obtain mucosal biopsy samples to measure the effect of the supplement on inflammatory and proliferative biomarkers of cancer risk, with follow-up assessments and data/specimen collection similar to baseline. Secondary outcome measures include the impact of a high fibre supplement on the oral and colonic microbiome and biofluid metabolome. ETHICS AND DISSEMINATION: Approvals were obtained from the Alaska Area and University of Pittsburgh Institutional Review Boards and Alaska Native Tribal Health Consortium and Southcentral Foundation research review bodies. A data safety monitoring board, material transfer agreements and weekly study team meetings provide regular oversight throughout the study. Study findings will first be shared with AN tribal leaders, health administrators, providers and community members. Peer-reviewed journal articles and conference presentations will be forthcoming once approved by tribal review bodies. TRIAL REGISTRATION NUMBER: NCT03028831.

Study of pathological complete response rate with neoadjuvant concurrent chemoradiation with paclitaxel in locally advanced breast cancer.

BACKGROUND: Neoadjuvant concurrent chemoradiation (CTRT) is not widely practiced in breast cancers. The current study presents our experience with the use of neoadjuvant CTRT in patients with locally advanced breast cancers (LABC) treated at our center. METHODS: The study included all consecutive female patients with inoperable stage III LABC treated at Cancer Institute (W.I.A), Chennai, India, from December 2015 to September 2016. Data were collected retrospectively from the patients' case records. The impact of neoadjuvant CTRT on the pathological complete response (pCR) and survival was analyzed. Neoadjuvant chemotherapy consisted of 4 cycles of adriamycin and cyclophosphamide given either before or after 4 cycles of paclitaxel. All chemotherapy cycles were given once in 3 weeks. Concurrent radiotherapy was incorporated with 2 cycles of paclitaxel. RESULTS: The study included 100 patients with a median age of 49 years, among whom 9 (9%) had IIIA disease, 73 (73%) IIIB, and 18 (18%) had IIIC disease. The hormone receptor-positive disease was observed in 36 (36%) patients, triple-negative in 24 (24%), and Her2/neu positive disease in 40 (40%) patients. All patients were operable after completing the planned neoadjuvant treatments. Ninety-one out of 100 (91%) patients underwent modified radical mastectomy whereas 9 (9%) did not consent for surgery. Among the patients who underwent MRM, 34/91 (37.7%) patients had a pCR. Moreover, pCR was observed in 12/22 (54.5%) patients with triple-negative disease, 10/34 (29.4%) patients with hormone receptor-positive disease, and 12/35 (34.2%) patients with Her2/neu positive disease (P = 0.19). Most common morbidity observed was grade 3 skin reactions. The 2-year event-free survival and overall survival for the entire cohort was 73.1% and 88%, respectively. CONCLUSION: Neoadjuvant CTRT is associated with a higher pCR rate than what has been reported with neoadjuvant chemotherapy alone. Further prospective studies are required to confirm our findings.

Neoadjuvant concurrent chemoradiation in male breast cancer: Experience from a tertiary cancer center.

BACKGROUND: Male breast cancers (MBC) account for 1% of all breast cancers. Neoadjuvant concurrent chemoradiation (CTRT) is not the standard of care for treating breast cancer. However, in our center, it has been routinely used in patients with locally advanced breast cancer to downsize the tumor and make it amenable to surgery. AIM: This study was conducted to examine the clinical and pathological profile and outcomes of patients with MBC treated at our institute with neoadjuvant CTRT. SETTINGS AND DESIGN: The study was conducted at a tertiary cancer center and was retrospective in nature. MATERIALS AND METHODS: All MBC patients treated with neoadjuvant CTRT at our center between 2001 and 2016 were enrolled in the study. Data were retrospectively extracted from the patients' case records. STATISTICAL ANALYSIS: Kaplan-Meier method was used for survival analysis and the outcome variables were compared using the log-rank test. RESULTS: Thirty-one MBC patients who received neoadjuvant CTRT were analyzed in this study. The median age of the patients was 53 years. Stage IIB disease was observed in 8/31 (26%) patients, stage III in 20/31 (64%), and stage IV in 3/31 (10%) patients. There was no grade 3 or 4 toxicity due to CTRT. Surgery was performed in 29/31 (94%) patients and none of the patients had a pathological complete response. The median duration of follow-up was 95.3 months. The 8-year event-free survival and overall survival for stage IIB, III, and IV were 75%, 50%, and 0% and 87.5%, 69%, and 0%, respectively. CONCLUSION: This is the first study to report on the use of neoadjuvant CTRT in MBC. Prospective evidence from phase-3 randomized controlled trials on the safety and efficacy of CTRT in breast cancer is required before its routine use can be recommended.

Vulvar skin atrophy induced by topical glucocorticoids.

Steroid-induced skin atrophy is the most frequent and perhaps most important cutaneous side effect of topical glucocorticoid therapy. To date, it has not been described in vulvar skin. A patient presented with significant vulvar skin atrophy following prolonged steroid application to treat vulvar dermatitis. The extensive atrophy in the perineum resulted in secondary "webbing" and partial obstruction of the genital hiatus and superimposed dyspareunia. Prolonged use of topical steroids may result in atrophic changes in vulvar skin. Further research in clinical correlates of steroid-induced atrophy in the vulvar region is warranted.

Psychosexual correlates of persistent postsurgical pain in patients with vulvodynia.

OBJECTIVE: To examine long-term reports of pain and psychologic correlates of pain in women after vestibulectomy. METHODS: In a retrospective cross-sectional exploratory study, 37 women who had undergone vestibulectomy between January 1989 and January 2008 completed questionnaires assessing demographic information, self-reported levels of pain, anxiety, somatization, psychologic distress, and sexual function. RESULTS: Eight women reported being completely pain free after surgery. The remaining 29 women reported various levels of pain during intercourse (as measured by the Gracely pain scale) and decreased sexual function (as measured by a sexual functioning questionnaire). Various measures of psychologic distress were associated with average intercourse-related pain, including brief symptom inventory (P=0.002), Pennebaker inventory of limbic languidness (P=0.002), perceived stress scale (P=0.04), and Spielberger trait-anxiety inventory (P=0.01). These same measures of psychological distress were similarly associated with general, unprovoked vaginal pain. CONCLUSION: The present data suggest that the pathophysiology of localized vulvodynia may be more complex in some women, leading to a suboptimal response to surgical treatment.

Cytogenetic investigation in chronic myeloid leukemia: study from an Indian population.

Chronic myeloid leukemia (CML) is a malignant neoplasm of hematopoietic cells characterized by abnormal proliferation of myeloid precursors, decreased rates of self destruction and an arrest in cellular differentiation. The bone marrow and peripheral blood accumulates all forms of mature and immature granulocytes, primarily blast cells. It is the most common type of leukemia seen in India, accounting for 30% of all leukemias. Cytogenetic analysis plays a vital and important role in the diagnosis of CML patients. The present study consists of cytogenetic evaluation of 175 CML cases from the Indian population with ages ranging from 6-86 years (mean of 42.8). The study population included 115 males (65.72%) and 60 females (34.28%) with a Male: Female ratio 1.9:1. Out of the 175 cases, 164 (93.7%) were successfully karyotyped while culture failure was observed for 11 (6.3%). Among the 164 reported cases, 53 (32.3%) showed a normal karyotype while within the 111 (67.7%) abnormal cases, 96 cases (86.5%) showed the presence of Philadelphia (Ph') chromosome with standard translocation t(9;22); Ph'+ve along with secondary aberrations was detected in 9 (8.1%) cases. Variants of Ph' chromosome were detected in only one case (0.9%). Ph'-ve CML with other chromosomal aberrations were detected in 5 (4.5%) cases, including +8, del 20q, del 11q and marker chromosome. Furthermore, we believe that availability of more advanced molecular techniques can be used as a supportive tool in CML diagnosis even though it cannot fully replace cytogenetics, which remains the backbone for laboratory investigation of the disease.