Effectiveness of triennial screening with clinical breast examination: 14-years follow-up outcomes of randomized clinical trial in Trivandrum, India.

BACKGROUND: This study presents the preliminary results of a randomized controlled trial (RCT) initiated in January 2006 in India to evaluate the effectiveness of clinical breast examination (CBE) in reducing breast cancer mortality as compared to a no-screening control group reported significant downstaging in the intervention group. The present manuscript reports long-term follow-up outcomes. METHODS: Women 30-69 years old from 133 intervention clusters and 141 control clusters were invited to participate. Women in the intervention arm underwent three rounds of CBE every 3 years. CBE-positive women were reexamined by a physician, and triple-assessment was performed on those confirmed to have abnormalities. All participants were followed through home visits and linkage with population-based cancer registry. RESULTS: Of the 55,843 eligible women in the intervention arm, 95.7% had CBE at least once and 11.5% were CBE-positive. Breast cancers were diagnosed in 335 participants in the intervention group and 273 in the control group (N = 59,447). Age-standardized incidence rate of early cancer was 30.4 of 100,000 in the intervention and 21.9 of 100,000 in the control group, with a rate ratio (RR) of 1.4 (95% confidence interval [CI], 1.1-1.8). The age-standardized breast cancer mortality rates were 11.3 and 11.1 per 100,000 in intervention and control arms, respectively (RR, 1.1; 95% CI, 0.8-1.5) after 15 years. Five-year breast cancer survival rates were 77.0% in the intervention and 71.2% in the control groups (overall p value = .043). CONCLUSIONS: Triennial CBE screening failed to demonstrate any mortality benefit despite achieving a shift toward earlier stage at detection and improved survival in the intervention arm. CBE is a valuable tool for diagnosis of breast cancer in symptomatic women especially in areas where mammography and/or breast cancer screening programs are not widely available.

Lifelong vegetarianism and breast cancer risk: a large multicentre case control study in India.

BACKGROUND: The lower incidence of breast cancer in Asian populations where the intake of animal products is lower than that of Western populations has led some to suggest that a vegetarian diet might reduce breast cancer risk. METHODS: Between 2011 and 2014 we conducted a multicentre hospital based case-control study in eight cancer centres in India. Eligible cases were women aged 30-70 years, with newly diagnosed invasive breast cancer (ICD10 C50). Controls were frequency matched to the cases by age and region of residence and chosen from the accompanying attendants of the patients with cancer or those patients in the general hospital without cancer. Information about dietary, lifestyle, reproductive and socio-demographic factors were collected using an interviewer administered structured questionnaire. Multivariate logistic regression models were used to estimate the odds ratio (OR) and 95% confidence intervals for the risk of breast cancer in relation to lifelong vegetarianism, adjusting for known risk factors for the disease. RESULTS: The study included 2101 cases and 2255 controls. The mean age at recruitment was similar in cases (49.7 years (SE 9.7)) and controls (49.8 years (SE 9.1)). About a quarter of the population were lifelong vegetarians and the rates varied significantly by region. On multivariate analysis, with adjustment for known risk factors for the disease, the risk of breast cancer was not decreased in lifelong vegetarians (OR 1.09 (95% CI 0.93-1.29)). CONCLUSIONS: Lifelong exposure to a vegetarian diet appears to have little, if any effect on the risk of breast cancer.

Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial.

BACKGROUND: For women with oestrogen receptor (ER)-positive early breast cancer, treatment with tamoxifen for 5 years substantially reduces the breast cancer mortality rate throughout the first 15 years after diagnosis. We aimed to assess the further effects of continuing tamoxifen to 10 years instead of stopping at 5 years. METHODS: In the worldwide Adjuvant Tamoxifen: Longer Against Shorter (ATLAS) trial, 12,894 women with early breast cancer who had completed 5 years of treatment with tamoxifen were randomly allocated to continue tamoxifen to 10 years or stop at 5 years (open control). Allocation (1:1) was by central computer, using minimisation. After entry (between 1996 and 2005), yearly follow-up forms recorded any recurrence, second cancer, hospital admission, or death. We report effects on breast cancer outcomes among the 6846 women with ER-positive disease, and side-effects among all women (with positive, negative, or unknown ER status). Long-term follow-up still continues. This study is registered, number ISRCTN19652633. FINDINGS: Among women with ER-positive disease, allocation to continue tamoxifen reduced the risk of breast cancer recurrence (617 recurrences in 3428 women allocated to continue vs 711 in 3418 controls, p=0·002), reduced breast cancer mortality (331 deaths vs 397 deaths, p=0·01), and reduced overall mortality (639 deaths vs 722 deaths, p=0·01). The reductions in adverse breast cancer outcomes appeared to be less extreme before than after year 10 (recurrence rate ratio [RR] 0·90 [95% CI 0·79­1·02] during years 5­9 and 0·75 [0·62­0·90] in later years; breast cancer mortality RR 0·97 [0·79­1·18] during years 5­9 and 0·71 [0·58­0·88] in later years). The cumulative risk of recurrence during years 5­14 was 21·4% for women allocated to continue versus 25·1% for controls; breast cancer mortality during years 5­14 was 12·2% for women allocated to continue versus 15·0% for controls (absolute mortality reduction 2·8%). Treatment allocation seemed to have no effect on breast cancer outcome among 1248 women with ER-negative disease, and an intermediate effect among 4800 women with unknown ER status. Among all 12,894 women, mortality without recurrence from causes other than breast cancer was little affected (691 deaths without recurrence in 6454 women allocated to continue versus 679 deaths in 6440 controls; RR 0·99 [0·89­1·10]; p=0·84). For the incidence (hospitalisation or death) rates of specific diseases, RRs were as follows: pulmonary embolus 1·87 (95% CI 1·13­3·07, p=0·01 [including 0·2% mortality in both treatment groups]), stroke 1·06 (0·83­1·36), ischaemic heart disease 0·76 (0·60­0·95, p=0·02), and endometrial cancer 1·74 (1·30­2·34, p=0·0002). The cumulative risk of endometrial cancer during years 5­14 was 3·1% (mortality 0·4%) for women allocated to continue versus 1·6% (mortality 0·2%) for controls (absolute mortality increase 0·2%). INTERPRETATION: For women with ER-positive disease, continuing tamoxifen to 10 years rather than stopping at 5 years produces a further reduction in recurrence and mortality, particularly after year 10. These results, taken together with results from previous trials of 5 years of tamoxifen treatment versus none, suggest that 10 years of tamoxifen treatment can approximately halve breast cancer mortality during the second decade after diagnosis. FUNDING: Cancer Research UK, UK Medical Research Council, AstraZeneca UK, US Army, EU-Biomed.

Comparison of imaging modalities for the accurate delineation of arteriovenous malformations (AVM) and evaluation of setup accuracy with reference to non-invasive LINAC-based stereotactic radiosurgery (SRS).

AIMS: To compare the accuracy of nidus delineation using magnetic resonance angiography (MRA) to digital subtraction angiography (DSA) and to evaluate setup accuracy of non-invasive frame SRS treatments. SETTINGS AND DESIGN: A prospective observational study of 16 patients who underwent non-invasive frame LINAC-based SRS for brain AVMs. MATERIALS AND METHODS: The nidus was separately delineated using DSA and MRA after co-registration onto CT simulation images and compared with respect to their volume and maximum diameters. During treatment, the setup errors observed in x-, y-, and z-directions were recorded. STATISTICAL ANALYSIS: Paired t-test (to compare volume and maximum diameter). Wilcoxon signed-rank test (for setup accuracy). RESULTS: The mean volume of nidus contoured in MRA was 4.16 cc compared to 3.11 cc in DSA (P 0.297). The mean maximum diameters using MRA and DSA, respectively, in antro-posterior, cranio- caudal, and transverse diameters were 21.97 cc vs. 19.46 cc (P 0.2380), 6.59 cc vs. 9.63 cc (P 0.161), and 18.87 cc vs. 16.81 cc (P 0.178). But these modalities can potentially misinterpret the nidus volume, warranting caution for use of either modality alone. The mean translational shift observed in the x-, y-, and z-directions were 0.06 mm, 0.13 mm, and 0.13 mm, respectively, when couch was brought to neutral position after clockwise couch rotation and 0.07, 0, and 0, respectively, after counterclockwise couch rotation. CONCLUSION: This study could not demonstrate any statistically significant differences in nidus delineation between MRA and DSA. Setup accuracy achieved with non-invasive thermoplastic mask-based immobilization is within acceptable limits for SRS.

Breastfeeding and breast cancer risk in India: a multicenter case-control study.

Breast cancer incidence is low in India compared with high-income countries, but it has increased in recent decades, particularly among urban women. The reasons for this pattern are not known although they are likely related to reproductive and lifestyle factors. Here, we report the results of a large case-control study on the association between breastfeeding and breast cancer risk. The study was conducted in 2 areas in South India during 2002-2005 and included 1,866 cases and 1,873 controls. Detailed information regarding menstruation, reproduction, breastfeeding and physical activity was collected through in-person interview. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by unconditional logistic regression models. Breastfeeding for long duration was common in the study population. Lifetime duration of breastfeeding was inversely associated with breast cancer risk among premenopausal women (p-value of linear trend, 0.02). No such protective effect was observed in postmenopausal women, among whom a protective effect of parity was suggested. A reduction of breast cancer risk with prolonged breastfeeding was shown among premenopausal women. Health campaign focusing on breastfeeding behavior by appropriately educating women would contribute to reduce breast cancer burden.

Quality of life determinants in women with breast cancer undergoing treatment with curative intent.

BACKGROUND: The diagnosis of breast cancer and its subsequent treatment has significant impact on the woman's physical functioning, mental health and her well-being, and thereby causes substantial disruption to quality of life (QOL). Factors like patient education, spousal support and employment status, financial stability etc., have been found to influence QOL in the breast cancer patient. The present study attempts to identify the determinants of QOL in a cohort of Indian breast cancer patients. PATIENTS AND METHODS: Functional Assessment of Cancer Therapy-Breast (FACT-B) Version 4 Malayalam was used to assess quality of life in 502 breast cancer patients undergoing treatment with curative intent. The data on social, demographic, disease, treatment, and follow-up were collected from case records. Data was analysed using Analysis of Variance (ANOVA) and multinomial logistic regression. RESULTS: The mean age of the patients was 47.7 years with 44.6% of the women being pre-menopausal. The FACT-B mean score was 90.6 (Standard Deviation [SD] = 18.4). The mean scores of the subscales were - Physical well-being 19.6 (SD = 4.7), Social well-being 19.9 (SD = 5.3), Emotional well-being 14 (SD = 4.9), Functional well-being 13.0 (SD = 5.7), and the Breast subscale 23.8 (SD = 4.4). Younger women (< 45 years), women having unmarried children, nodal and/or metastatic disease, and those currently undergoing active treatment showed significantly poorer QOL scores in the univariate analysis. However multivariate analysis indicated that the religion, stage, pain, spouse education, nodal status, and distance travelled to reach the treatment centre as indicative of patient QOL. CONCLUSION: QOL derangements are common in breast cancer patients necessitating the provisions for patient access to psychosocial services. However, because of the huge patient load, a screening process to identify those meriting intervention over the general population would be a viable solution.

Pneumocystis carinii pneumonia prophylaxis in HIV negative patients with primary CNS lymphoma.

Primary central nervous system lymphoma (PCNSL) is an uncommon malignant brain tumor, which is increasing in incidence in immunocompetent individuals. In the recent past, the survival at 5 years was less than 5% when this cancer was treated with radiation therapy and standard chemotherapy. Current high dose methotrexate-based regimens have resulted in median survival of 3-4 years and the 5-year survival approaches 40%. However, these potentially curable patients appear to be at significant risk for developing Pneumocystis carinii pneumonia (PCP), which has a mortality of nearly 50%. The major risk factors in this patient population appear to be glucocorticoids, high dose methotrexate, and radiation therapy all of which reduce CD4+ counts. Prophylaxis must be considered carefully because of the significant risk of drug interactions between the methotrexate and the antibiotics used to prevent Pneumocystis infections. This manuscript reviews the changing therapy for primary CNS lymphomas, the pathogenesis, diagnosis and treatment of P. carinii pneumonia, the potential interactions between methotrexate and prophylactic antibiotics, and the risk of Pneumocystis infection in these patients. It also provides recommendations for Pneumocystis prophylaxis for this patient population.

Clinicopathological significance of tissue homeostasis in Indian breast cancer.

BACKGROUND: Tissue homeostasis and the maintenance of cell populations depend on a delicate balance between the rates of cell proliferation and cell death. Disruption of this balance is an important factor in development and progression of tumors. In the present study we evaluated the growth index in a large group of breast cancer patients and correlated it with various clinical and histopathological features of the tumor. METHODS: Estimation of apoptosis was determined by TUNEL assay while immunocytochemistry for proliferating nuclear cell antigen (PCNA) was used as a measure of proliferation. Necrosis was identified morphologically by haematoxylin and eosin staining. RESULTS: A positive correlation was observed between the percentage of PCNA positive cells and the frequency of mitosis (r=0.6117, p<0.0001). A highly statistical significant correlation was observed between type of tissue analyzed and growth index (r=0.46869, p<0.0001). No significant association was observed between hormone receptor status and growth index. CONCLUSIONS: The growth index was found to be higher in carcinoma cells that metastasised into lymph nodes compared with primary lesions with no nodal metastasis. Growth index was particularly prominent in high-grade tumors in which increased proliferative activity was evident. Apoptotic cells were detected more frequently in tumor cells with higher rather than lower proliferative activity. This suggests that not only proliferative activity but also capacity for apoptosis is altered in breast tumors.

Initial response to glucocorticoids.

BACKGROUND: Known prognostic variables in patients with primary central nervous system lymphomas (PCNSL) include age, Karnofsky performance status, involvement of deep regions of the brain, intensity of blood-brain barrier disruption, and treatment with radiation and chemotherapy. PCNSL often responds transiently to glucocorticoids administered to control neurologic symptoms before radiation or chemotherapy. This retrospective chart review was designed to estimate the prognostic significance of a clinical or radiologic response to initial glucocorticoid therapy. METHODS: By using data from The Johns Hopkins Cancer Registry from January 1980 to June 2001, a total of 76 human immunodeficiency virus (HIV)-negative adults with newly diagnosed PCNSL were identified. Nineteen patients with uninformative medical records were excluded from the study. RESULTS: The median survival of the remaining 57 patients was 11.8 months. The median survival for the 48 patients who had clinical response to initial steroid therapy was 17.9 months, and for nonresponders, it was 5.5 months (P = 0.05). The 16 patients with documented radiologic response had a median survival of 117.0 months compared with 5.5 months for nonresponders (P = 0.001). After adjusting for known prognostic factors (age and treatment), significant reduction in risk of death was noted in patients who had either clinical (hazard ratio [HR] = 0.40; 95% confidence interval [CI], 0.16-0.99}) or radiologic response (HR = 0.14; 95% CI, 0.04-0.46) to glucocorticoids given before radiation or chemotherapy. CONCLUSION: This analysis suggests that initial response to treatment with glucocorticoids may be an important prognostic factor in patients with PCNSL.