Nita Nair

Abstract S2-02: Surgical removal of primary tumor and axillary lymph nodes in women with metastatic breast cancer at first presentation: A randomized controlled trial

BACKGROUND: The role of loco-regional treatment, in women with metastatic breast cancer (MBC) at first presentation, is debatable. Preclinical evidence suggests that such treatment may facilitate growth of metastatic disease. On the other hand, many retrospective analyses in clinical cohorts have suggested favorable impact of loco-regional treatment in these patients. However, these results are likely to be influenced by selection bias. We conducted a prospective randomized controlled trial to assess the impact of loco-regional treatment on outcome in women with metastatic breast cancer at initial diagnosis. [NCT00193778] METHODS: Women with metastatic breast cancer at initial diagnosis and planned to be treated with anthracycline based chemotherapy (CT) were registered for the study. Those who had objective tumor response after 6 cycles of CT were randomized to one of the following arms: ‘LRT’ (loco-regional treatment) or ‘No-LRT’ (no loco-regional treatment). Patients were stratified by endocrine receptor (ER) status, site of metastases (visceral Vs bone Vs both) and number of metastatic lesions ( 3). Women in LRT arm received surgery (breast conservation or mastectomy plus axillary lymph node dissection) followed by radiation therapy (RT), as per standard adjuvant guidelines. Women in No-LRT arm were followed up without surgery and RT. Both groups received standard endocrine therapy after last cycle of chemotherapy, if indicated. They were regularly followed up with clinical evaluation. Appropriate imaging was performed within 6 months after randomization and thereafter as clinically indicated. The primary endpoint was overall survival (OS). RESULTS: Between Feb 2005 and Jan 2013, 350 women were randomized, 173 in LRT and 177 in No-LRT arm. The data cutoff was in May 2013. The two arms were balanced with respect to age, clinical tumor size, HER2 receptor status and stratification factors. Eight (5.8%) patients in the LRT arm did not undergo loco-regional therapy while 19 (10.7%) patients in the No-LRT arm underwent surgical removal of primary tumor because of palliative reasons. The median follow-up was 17 months and 218 deaths (LRT = 111/173, No-LRT = 107/177) had been recorded at data cutoff. The median OS in LRT and No-LRT arms were 18.8 and 20.5 months (HR = 1.07, 95%CI = 0.82-1.40, p = 0.60) and the corresponding 2-year OS were 40.8% and 43.3%, respectively. After adjusting for age, ER status, HER2 receptor status, site of metastases and number of metastatic lesions in a Cox regression model, there was no significant difference in OS between LRT and No-LRT arms (HR = 1.00, 95%CI = 0.76-1.33, p = 0.98). There was no interaction between the effect of LRT and covariates in the model. CONCLUSIONS: Loco-regional treatment of the primary tumor and axillary nodes has no impact on OS in patients diagnosed with MBC at initial presentation, who have responded to frontline chemotherapy. We were unable to identify any subgroups that are likely to benefit from LRT. Such treatment should be reserved for women who need it for palliative reasons. Detailed analysis will be presented at the Symposium. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr S2-02.

Estrogen, progesterone and HER2 receptor expression in breast tumors of patients, and their usage of HER2-targeted therapy, in a tertiary care centre in India

BACKGROUND This study was undertaken to document the pattern of expression of estrogen (ER), progesterone (PR) and human epidermal growth factor receptor-2 (HER2) and the usage of HER2-targeted therapy in a large tertiary care hospital in India in the year 2008. MATERIALS AND METHODS The histopathology reports of all breast cancer patients registered in the hospital in 2008 were extracted from the electronic medical record system. All the cases were immunohistochemically evaluated for estrogen and progesterone receptor status (ER and PR), and c-erbB-2 protein (HER2) expression using standard immunoperoxidase method. The use of HER2-targeted therapies was evaluated by extracting relevant information from the database of the hospital pharmacy and case charts of patients enrolled in ongoing approved trials. RESULTS A total of 2001 new patients of invasive breast cancers with available pathology reports were registered in the hospital in the year 2008. ER and/or PR expression was positive in tumors of 1025 (51.2%) patients. HER2 3+ expression by immunohistochemistry (IHC) was found in 335 (16.7%) and HER2 2+ in 163 (8.1%). The triple negative phenotype was found in 596 (29.8%) patients. An estimated 441 patients were eligible to receive HER2-targeted therapy based on their HER2 status. Of these 38 (8.6%) patients received some form of HER2-targeted therapy; 20 patients (4.5%) as part of ongoing clinical trials and 18 (4.1%) as part of routine care. CONCLUSIONS The overwhelming majority of patients eligible for HER2-targeted therapy in our institution are unable to receive it because of financial constraints and limited access to health insurance. There is a higher fraction of patients with the triple negative phenotype compared to the Western population.

Papillary thyroid carcinoma with exuberant nodular fasciitis-like stroma: treatment outcome and prognosis

Papillary thyroid carcinoma with nodular fasciitis-like stroma (PTC-NFS) is one of the extremely rare variants of papillary thyroid carcinoma. To date, the majority of reported cases have been published in the surgical pathology and cytopathology literature, addressing the diagnostic difficulties posed by the conditions extensive, reactive stromal proliferation. Because of the rarity of PTC-NFS among papillary thyroid carcinoma variants, it has been unexplored from a clinical viewpoint. A MEDLINE search on the clinical course, role of radioiodine, treatment outcome and long term follow up of this disease yielded no result.We report the clinicoradiologic and histopathologic profile, together with post-treatment long term follow up, in a 35-year-old woman harbouring this rare entity. To the best of our knowledge, this is the first report of a five-year follow up of this rare variant of PTC following total thyroidectomy and radioiodine treatment. Our follow-up findings reiterate the diseases favourable clinical course when managed in the same manner as a classical, differentiated papillary carcinoma of the thyroid, akin to that predicted by the pathologists, and emphasize the importance of differentiating PTC-NFS as a separate entity from the papillary carcinoma variants with aggressive histology. Given the rarity of this condition, the experience gained from the present case is a useful addition to the current knowledge on disease prognostication and management.A systematic review of the existing literature on PTC-NFS, including the case reported in the present paper, is also carried out, aiming to explore the patient characteristics and clinical behaviour pattern of this rare entity and to make appropriate recommendations on management strategy. The age of presentation ranges from 20 to 82 years, with a mean of 44.5 years. Female preponderance was observed, with a female to male ratio of 3ratio1. No racial predilection was observed. Tumour size varied from 2 to 9 cm along its greatest diameter (mean = 4.3 cm). Metastasis to lymph nodes at presentation occurred in 25 per cent of cases. Metastasis to surrounding structures (e.g. parathyroid and skeletal muscle) was observed in 12.5 per cent. There have been no reports of pulmonary or skeletal metastasis at presentation.

Impact of adjuvant radiation therapy photon energy on quality of life after breast conservation therapy: Linear accelerator versus the cobalt machine

BACKGROUND Breast conservative therapy (BCT) is a standard treatment option in early operable breast cancers (OBC) and a select group of large or locally advanced tumors. The present study deals with prospective evaluation of quality of life (QOL) score in consecutive patients treated with BCT employing adjuvant RT treated with either a cobalt machine or a linear accelerator (LA). MATERIAL AND METHODS Patients of carcinoma breast who underwent BCT were taken into the study. Patients with larger breasts (inter-field separation >18-20 cm) were treated on LA and those with smaller breasts were treated on cobalt machine. All patients received a uniform RT dose (45-50 Gy/25#/5 weeks) to whole breast followed by tumor bed boost with suitable energy electrons. Prospective evaluation of QOL was done using EORTC QLQ C30 and breast cancer-specific EORTC QLQ BR23. QOL evaluation was done at pre-RT, at half completion of RT treatment (at 20-23 fractions) and at completion of RT. RESULTS Pre-RT evaluation GQOL scores in patients treated with cobalt and LA were 71.6 and 71.7, respectively (P = 0.8). QLQ C30 functional and symptom domain scores were also similar in the groups. At RT completion, Global quality of life (GQOL) scores were 67.7 in patients treated with cobalt as compared to 77.7 in patients treated with LA (P = 0.75). Physical function domain scores in cobalt and LA patients were 70.8 and 80.3, respectively (P = 0.26). Fatigue score was higher in patients treated with cobalt (39.1 versus 29.7; P = 0.9). However, there was no difference in other functional and symptom domains. There was no significant change in any of the EORTC QLQ C30 domains at RT completion as compared to the pre-RT scores. CONCLUSION There is no significant difference in QOL domains between appropriately selected patients treated with cobalt and LA. There are no significant changes in QOL domain scores at RT conclusion as compared to pre-RT baseline in patients treated with cobalt or LA source. A cobalt machine may be effectively used to deliver adjuvant RT in appropriately selected BCT patients especially in developing countries with limited resources.

Paradigm shift in surgery for breast cancer: The Indian reality

The latter part of the last millennium was a period of new discoveries in science and medicine, with a new understanding of the cause and treatment of cancer in general. Over the years, there has been a paradigm shift toward more conservative surgery in the treatment for breast cancer. However, despite conclusive level one evidence for the safety of breast conserving surgery (BCS),[1] the Indian surgeon continues to debate the most appropriate surgery for the primary tumor. The authors rightly mention that BCS is not a popular choice among surgeons in India (11–23% versus 60– 70% in the west) as compared with data cited from the west. Many previous studies evaluating the acceptance of breast conservation have cited patients’ psychologic distress associated with fear of recurrence as a factor in not recommending BCS.[2]

A Prospective Study of Computerized Digital Infrared Image Analysis (NoTouch BreastScanTM) in Biopsy Proven Breast Cancers.

Introduction: Early detection of breast cancer is known to have a more favourable outcome. Currently clinical breast examination and imaging modalities, primarily mammography are used for screening purposes. In India, more than 85% of the population is below the age of 50 years, wherein the sensitivity of mammography is at best 64%. Additional drawbacks of the procedure are physical discomfort and ionizing radiation dose to the patient. So newer techniques have been investigated which detect cancer induced neovascularity with digital thermal imaging. The purpose of this clinical study was to determine the efficacy of a software assisted thermal image analysis tool to distinguish between benign and malignant lesions of the breast.Methods: A prospective study was conducted in women who presented to the breast clinic with clinically or mammographically suspicious breast lesions. They also underwent thermal imaging of the breast. All mammographically suspicious lumps were subjected to histopathological confirmation. The mammography and infrared (IR) reports were compared to the histopathology.Results: In 90 women, 180 breasts were independently analyzed by both digital IR software analysis and mammography. Eighty five out of these 180 had suspicious lesions on mammography or clinical examination which were subjected to pathological confirmation. Mammography being the present diagnostic gold standard, all normal mammograms in clinically normal breast were considered as non-malignant. The sensitivity and specificity of digital thermography in detecting malignant lesions was 88.24% and 70.52% respectively with NPV of 87.01% and PPV of 72.82%. While for mammography the sensitivity and specificity were 96.25% and 96.7% with NPV of 96.7% and PPV of 96.25%. In women below 50 years of age (62/90) the sensitivity and specificity of digital thermography was 89.83% and 64.61% with NPV of 87.5% and PPV of 69.74%. Further, in the same subset no statistically significant difference was detected in the sensitivity of digital thermography to that of mammography (p = 0.7263).Conclusion: Our initial experience shows that the detection rate by digital thermal imaging is comparable to mammography in clinically palpable breast tumors. We also note that there is no significant difference in sensitivity of thermal imaging in women on either side of 50 making it a potentially testable tool for screening in younger women. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5028.

Should molecular subtype be recommended as one of the selection criteria for accelerated partial breast irradiation? Preliminary results from an Asian cohort

Purpose The purpose of this study was to report clinical outcomes in patients treated with accelerated partial breast irradiation (APBI), stratified as per molecular subtype and American Society for Therapeutic Radiology and Oncology/Groupe Européen de Curiethérapie and European Society for Radiotherapy & Oncology (ASTRO/GEC-ESTRO) patient selection criteria in order to determine whether molecular subtype should be recommended as one of the selection criteria for APBI. Material and methods 157 early-stage breast cancers patients, treated with APBI using multi-catheter interstitial brachytherapy with ≥ 6 months follow-up were included. Molecular subtype was assigned based on estrogen/progesterone receptor (ER/PR), Her2neu and tumor grade. Patients were stratified into ASTRO and GEC-ESTRO risk groups, as per updated ASTRO consensus statement (CS) and GEC-ESTRO recommendation, respectively. The Kaplan-Meier method was used to calculate the time to event data of clinical outcomes. Results With a median follow-up of 35 months, local control (LC) and locoregional control (LRC) were not significantly different among the different molecular subtypes (p = 0.19, p = 0.41, respectively). None of the APBI guidelines predicted risk of local or locoregional recurrence. Re-analyzing the data by replacing ER status with molecular subtype in the ASTRO-CS did not show any significant difference in LC/LRC across the various categories. Her2neu subtype was associated with significantly lower disease-free survival, cause specific survival, and overall survival than the luminal subtypes. Conclusions None of the mentioned APBI guidelines predicted local or locoregional recurrence risk in our study population. Additional follow-up will be needed to recommend inclusion of molecular subtype (or at least HER2 receptor status) in the patient selection criteria for APBI.

Imaging of the treated breast post breast conservation surgery/oncoplasty: Pictorial review

Mammographic appearance of the normal breast is altered in the post-operative setting. It is essential to be aware of the normal findings as well as to identify features of recurrent disease with particular emphasis on radiological-pathological concordance. Digital breast tomosynthesis and volumetric breast density add incremental value in this clinical setting. We present a pictorial review of various cases to illustrate normal post-operative findings as well as mammographic features suspicious for recurrent disease.

Metastatic nasopharyngeal carcinoma presenting as an isolated breast mass: A diagnostic pitfall and a review of literature

Metastases to breast are much rarer than primary breast tumors. We now present a case of 45-year-old female, who presented with an isolated breast mass. A positron emission tomography-computed tomography (PET-CT) done revealed hypermetabolic right breast nodules, soft tissue deposits, and multiple nodal involvement. The biopsy from the breast and axillary lymph node showed dense lymphoid infiltrate and was interpreted initially as granulomatous inflammation. However, the lumps were hard and suspicious for primary breast cancer, so an immunohistochemistry for cytokeratin was performed which highlighted the epithelial cell clusters masked within the inflammatory infiltrate and the diagnosis of undifferentiated carcinoma, lymphoepithelioma-like was made. After the diagnosis was made, it was realized that the patient had been treated earlier for a nasopharyngeal carcinoma (NPC). The in situ hybridization (ISH) test for Epstein–Barr virus-encoded RNA ISH was positive in the tumor cells, and hence, a diagnosis of metastatic NPC was finally made. The patient subsequently developed extensive nodal, skeletal, and soft tissue metastatic disease but was alive till September 2015. Although extremely rare, metastatic NPC can occur in the breast and the above case highlights that it mimics an inflammatory lesion. This case highlights the importance of the multidisciplinary approach for appropriate tumor diagnosis and patient management.

Bilateral breast cancer following multimodality treatment- A report of clinical outcome in Asian population

&NA; Literature on clinical outcome of bilateral breast cancer (BBC) from Indian subcontinent is sparse. In this institutional series of 193 BBC, it was seen that synchronous presentation was more common. Metachronous tumors differ from synchronous with higher grade at presentation and less expression of estrogen receptor. There was no difference in outcome between patients with synchronous and metachronous tumors. Background: Bilateral breast cancer (BBC) is an uncommon presentation. The characteristics and outcomes of synchronous and metachronous BBC were compared within an Indian cohort. Patients and Methods: This was a retrospective audit of 193 BBC patients treated at a tertiary hospital in India over a period of 10 years from January 2004 to December 2014. The demographic, tumor and treatment characteristics were compared between synchronous (n = 131 patients) and metachronous tumors (n = 62 patients) using descriptive analysis. The survival outcomes were assessed using Kaplan–Meier survival curves and compared using the log rank test. Univariate and multivariate analysis was done using a Cox proportional hazards model to assess the effect of the prognostic factors on survival. Results: The mean age of presentation in synchronous BBC (SBBC) and metachronous BBC (MBBC) was 55 years (SD, 12.5) and 51 years (SD, 9.5), respectively. The median time to contralateral presentation in MBBC was 3.8 years. Mean tumor size was larger in SBBC (P = .01). Breast Cancer gene mutation was positive in 13 of 38 evaluated patients (of whom 12 had MBBC). The concordance rates for the estrogen receptor (ER) and progesterone receptor negativity and triple‐negative receptor status were higher in MBBC compared with SBBC (P < .001). Grade III tumor was more frequently seen in MBBC (P = .03). The median follow‐up of the entire cohort was 42 months (range, 30‐60 months): 45 months for SBBC and 35 months for MBBC. The 3‐year rates of overall survival (OS), disease‐free survival (DFS), and locoregional control (LRC) for SBBC and MBBC was 88% and 90%, 74% and 64% and 90% and 84%, respectively. There was no difference in overall OS, DFS, and LRC between SBBC and MBBC. Conclusion: BBC is an uncommon presentation. Synchronous presentation was more common. Metachronous tumors differ from synchronous with higher Grade of presentation and less expression of ER. There was no difference in outcome between patients with synchronous and metachronous tumors.