Budhi Singh Yadav

Systemic treatment strategies for triple-negative breast cancer

Triple-negative breast cancer (TNBC) is defined by the lack of immunohistochemical expression of the estrogen and progesterone receptors and human epidermal growth factor receptor 2 (EGFR2). Most TNBC has a basal-like molecular phenotype by gene expression profiling and shares clinical and pathological features with hereditary BRCA1 related breast cancers. This review evaluates the activity of available chemotherapy and targeted agents in TNBC. A systematic review of PubMed and conference databases was carried out to identify randomised clinical trials reporting outcomes in women with TNBC treated with chemotherapy and targeted agents. Our review identified TNBC studies of chemotherapy and targeted agents with different mechanisms of action, including induction of synthetic lethality and inhibition of angiogenesis, growth and survival pathways. TNBC is sensitive to taxanes and anthracyclins. Platinum agents are effective in TNBC patients with BRCA1 mutation, either alone or in combination with poly adenosine diphosphate polymerase 1 inhibitors. Combinations of ixabepilone and capecitabine have added to progression-free survival (PFS) without survival benefit in metastatic TNBC. Antiangiogenic agents, tyrosine kinase inhibitors and EGFR inhibitors in combination with chemotherapy produced only modest gains in PFS and had little impact on survival. TNBC subgroups respond differentially to specific targeted agents. In future, the treatment needs to be tailored for a specific patient, depending on the molecular characteristics of their malignancy. TNBC being a chemosensitive entity, combination with targeted agents have not produced substantial improvements in outcomes. Appropriate patient selection with rationale combinations of targeted agents is needed for success.

Biomarkers in triple negative breast cancer: A review

Breast cancer is an intrinsically heterogeneous disease. In the world about 1 million cases of breast cancer are diagnosed annually and more than 170000 are triple-negative. Characteristic feature of triple negative breast cancer (TNBC) is that it lacks expression of oestrogen, progesterone and human epidermal growth factor receptor-2/neu receptors. They comprise 15%-20% of all breast cancers. We did a systematic review of PubMed and conference databases to identify studies published on biomarkers in TNBC. We included studies with biomarkers including: Epidermal growth factor receptor, vascular endothelial growth factor, c-Myc, C-kit and basal cytokeratins, Poly(ADP-ribose) polymerase-1, p53, tyrosinase kinases, m-TOR, heat and shock proteins and TOP-2A in TNBC. We also looked for studies published on synthetic lethality and inhibition of angiogenesis, growth, and survival pathways. TNBC is a complex disease subtype with many subclasses. Majority TNBC have a basal-like molecular phenotype by gene expression profiling. Their clinical and pathologic features overlap with hereditary BRCA1 related breast cancers. Management of these tumours is a challenge to the clinician because of its aggressive behaviour, poor outcome, and absence of targeted therapies. As the complexity of this disease is being simplified over time new targets are also being discovered for the treatment of this disease. There are many biomarkers in TNBC being used in clinical practice. Biomarkers may be useful as prognostic or predictive indicators as well as suggest possible targets for novel therapies. Many targeted agents are being studied for treatment of TNBC.

Nonbreast Second Malignancies After Treatment of Primary Breast Cancer

PURPOSE To determine the incidence and risk factors for nonbreast second malignancies (NBSMs) in women after treatment for primary breast cancer. METHODS AND MATERIALS Between January 1985 and December 1995, a total of 1,084 breast cancer patients were analyzed for NBSMs. Detailed analysis was carried out for age, family history, disease stage, radiation therapy, chemotherapy, hormone therapy, other clinical/pathologic characteristics, and site of NBSMs. The Cox proportional hazard regression model was used to estimate the relative risk of NBSMs. RESULTS Median follow-up was 12 years. In total, 33 cases of NBSMs were noted in 29 patients. The overall incidence of NBSM was 3%, and the median time for NBSMs was 7 years. The most common NBSMs were gynecologic (22 patients), gastrointestinal (4 patients), head and neck (3 patients), hematologic (2 patients), lung (1 patient), and thyroid (1 patient). The NBSMs rate at 12 years was 2.4% for both mastectomy and radiation therapy groups. In the subset of patients less than 45 years of age at the time of treatment, the NBSMs rate was 0.7% as compared with 4.6% in patients more than 45 years of age (p = 0.001). Statistically significant higher incidences of endometrial and ovarian cancer were seen in patients with hormonal therapy (5.2%) as compared with patients without hormonal therapy (1.8%, p = 0.002). Women with a family history of breast cancer had a higher incidence (6%) of endometrial and ovarian malignancy compared with women without such a history (2.1%, p = 0.003). Chemotherapy did not affect the risk of second malignancy. CONCLUSION The most common NBSMs in this study were gynecologic. Family history of breast cancer was a high risk factor for NBSMs. No risk of NBSMs with radiotherapy was observed.

Postmastectomy radiation and survival in patients with breast cancer

PURPOSE To analyze the impact of postmastectomy radiotherapy on locoregional control and overall survival in patients with carcinoma breast. MATERIALS AND METHODS Between 1995 and 2000, 688 patients of carcinoma breast were analyzed. Out of these, 608 received postmastectomy radiotherapy and 80 patients were not given any radiation therapy. At a median follow-up of 67 months, the outcomes studied were locoregional recurrence (LRR), distant metastases, disease-free survival (DFS) and overall survival (OS) using univariate and multivariate analyses. RESULTS The frequency of LRR with or without distant metastases was 8.5%, and distant metastases was seen in 18.7% of patients. On univariate analyses, factors affecting LRR were age < 40 years (0.019), tumor stage ( P = 0.001 ), grade ( P = 0.027 ), pathological nodal status ( P ), deep resection plane (0.041), ER/PR status ( P = 0.032 ) and postmastectomy radiation therapy (PMRT) ( P ). DFS rate was 69% at 5 years. Factors affecting distant metastases were age < 40 years (0.005), tumor stage ( P ), grade ( P = 0.0007 ), pathological nodal status ( P ), extra capsular extension (ECE) ( P = 0.002 ), hormonal therapy ( P ) and PMRT ( P ). The OS rate was 81% at 5 years. Factors affecting OS were tumor stage ( P ), grade ( P = 0.0001 ), pathological nodal status ( P ), ECE ( P = 0.002 ) ER/PR status ( P = 0.008 ), hormonal therapy ( P = 0.001 ) and PMRT ( P = 0.004 ). On multivariate analysis, factors affecting LRR were age ( P = 0.001 ), tumor stage ( P = 0.021 ), deep resection plane (0.003), ECE ( P = 0.022 ) and PMRT ( P = 0.047 ). Factors affecting distant metastases were menopause ( P = 0.044 ), grade ( P = 0.012 ), ECE ( P = 0.017 ) and PMRT ( P = 0.012 ). Factors affecting OS were menopausal status ( P = 0.017 ), tumor stage ( P = 0.029 ), pathological nodal status ( P = 0.011 ) and PMRT ( P = 0.002 ). CONCLUSION PMRT improves LRR as well as OS in patients with carcinoma breast. Other factors of prognostic importance were menopausal status, tumor stage and pathological nodal status.

Pediatric Astroblastoma: A Rare Case with a Review of the Literature

Astroblastoma is a rare glial tumor with uncertain histopathological origin and unpredictable clinical behavior. We present a case of an 11-year-old girl who presented with headache and blurring of vision for 2 months. A well-demarcated mass was found in the right frontoparietal lobe on a brain MRI. The patient was treated with total tumor resection followed by postoperative radiotherapy. Histologically, the features were suggestive of high-grade astroblastoma. The patient is alive and disease free 23 months after surgery. The characteristic radiological and histopathological features and treatment of this case are described with a literature review.

Paraneoplastic leukocytoclastic vasculitis in chronic lymphoid leukemia

A 50-year-old female who was a known case of chronic lymphoid leukemia (CLL) developed ecchymoses, purpuric spots with papules, some nodules (1-3 mm) and crusts all over the body associated with severe burning and itching along with exaggeration of CLL. The lesions were more prominent on lower limbs and face. Skin biopsy was reported as leukocytoclastic vasculitis. These lesions regressed after treatment with leukeran and glucocorticoids.

Carcinoma lung presenting with choroidal metastasis as initial presentation: a rarity.

Diminished vision due to choroidal metastasis as the primary symptom of lung cancer is very uncommon. Here, we report such a presentation in a 54-year-old male patient of small cell lung cancer. The outcome is usually dismal with this kind of presentation. The patient received systemic chemotherapy as well as intravitreal bevacizumab but with no improvement in vision. The patient had been given external beam radiotherapy and showed subjective improvement in his ocular symptoms.

Outcome of neoadjuvant chemotherapy in locally advanced breast cancer: A tertiary care centre experience.

Background: Introduction of neoadjuvant chemotherapy (NACT) has dramatically changed the management of locally advanced breast cancer (LABC). However, very few randomized trials of NACT have been carried out specifically in LABC patients in our country. In this retrospective analysis, we presented our experience with NACT in LABC patients. Materials and Methods: Medical records of 148 patients of stage III LABC patients treated with NACT, followed by surgery and radiotherapy from January 2006 to December 2010 were reviewed. Clinical and pathological responses to different chemotherapy regimens were assessed according to World Health Organization criteria. Various factors influencing response to NACT and clinical outcome were identified and analyzed. Results: A total of 90 (60.8%) patients received anthracycline-based chemotherapy and 52 (35.1%) patients received mixed anthracycline and taxane-based chemotherapy.119 patients (80.4%) responded to NACT either in the form of complete or partial response (PR). Complete response was seen in 27 (18.2%) patients and 92 (62.2%) patients showed PR after NACT. Pathological complete response was seen in 24 (16.2%) patients-. At a median follow-up period of 44 months 36 patients (24.3%) developed relapse of which six patients developed locoregional recurrence, while 28 (18.9%) patients developed distant metastasis. Nodal status, response to chemotherapy, pathological tumor size <3 cm and extracapsular extension (ECE) came out to be important prognostic factors in this study. Conclusion: Neoadjuvant chemotherapy is a reasonable alternative to upfront surgery in the management of LABC. Clinicopathological variables such as nodal status, response to chemotherapy, pathological tumor size and presence of ECE had significant impact on disease free survival.

Low-grade myofibroblastic sarcoma of the larynx: A rare entity with review of literature

Mesenchymal neoplasms of the larynx are rare and make up approximately 0.3% to 1.0% of all malignancies at this location. Low grade myofibroblastic sarcoma (LGMS) of larynx is a rare entity. We describe a rare case of LGMS of larynx who presented with complaint of hoarseness of voice. The patient was treated with total laryngectomy plus partial pharyngectomy followed by post-operative radiotherapy. Histopathologically, the lesion was composed of spindle cells that manifested variable cellular anaplasia and expressed smooth muscle actin (SMA) and focally S-100.One of the resection limits was involved so patient was given post-operative radiotherapy. The patient is alive and disease free 14 months after surgery. The characteristic clinical, histopathological features and treatment of this case are described with a literature review.

Results of letrozole in postmenopausal women after tamoxifen treatment for advanced breast cancer

AIM To analyze overall and progression-free survival after letrozole in postmenopausal women with advanced breast cancer who failed after tamoxifen therapy. MATERIALS AND METHODS This is a retrospective analysis of 95 patients with breast cancer who were postmenopausal and had failed after tamoxifen therapy. Dose of letrozole was 2.5 mg daily until disease progressed. Patients had estrogen receptor- and/or progesterone receptor-positive tumors or both receptors were unknown. One complete course of (6 cycles) chemotherapy for metastatic disease was allowed. The primary end point was time to progression (TTP). Secondary end points included overall objective response rate (ORR), its duration, time to treatment failure (TTF), overall survival and tolerability. RESULTS Median TTP was 10 months. ORR was 21% with complete response rate of 9%. Nine patients died of disease during treatment. Median overall survival was 36 months. Median time to response was three months and median duration of response was 13 months. Time to chemotherapy was 13.5 months and TTF was 9.3 months. Treatment failure was seen in 76% of patients. Disease progression was the main cause for treatment failure. Treatment was well-tolerated by all patients. CONCLUSION This retrospective analysis shows that letrozole is quite effective as second line therapy in postmenopausal patients with advanced breast cancer who had failed after tamoxifen therapy.