COVID-19 Impact on Newly Diagnosed Breast Cancers at Regional Cancer Centre, Thiruvananthapuram-An Audit.

Geethu Babu The coronavirus pandemic has created havoc in every aspect of life including cancer care and was declared a pandemic. This audit was conducted to study the impact of the pandemic on diagnosis and treatment of newly diagnosed breast cancer patients at a tertiary cancer center in South India. A total of 1,647 patients who registered at Regional Cancer Centre (RCC), Thiruvananthapuram, Kerala, India for breast cancer during the period April 1, 2020, to September 30, 2020 (COVID-19 period) as well as April 1, 2019, to September 30, 2019 (pre-COVID-19 period) were included in the study. Data regarding the geographic distribution, stage at presentation, time factors for reporting for care, diagnosis, and treatment, referral for care elsewhere were collected and analyzed. The study was approved by the Institutional Review Board. Means and ranges were calculated for continuous type variables, and numbers and percentages for categorical variables. To determine whether there were significant differences between the two groups, independent t -test was used for continuous variables and chi-square test for categorical type of variables. A notable reduction (36%) in newly diagnosed breast cancer patients was seen in 2020 when compared with 2019. There was a significant difference in the geographic distribution of patients in both cohorts ( p = 0.001) and a notable reduction in the number of patients reporting to RCC for treatment from the northern districts of Kerala (81%) and outside Kerala (89.5%). There was no significant difference in the time (in weeks) since symptom onset and reporting to hospital or the clinical stage at diagnosis between the groups. Also, coronavirus disease 2019 (COVID-19) did not seem to negatively impact time intervals between date of registration and pathological diagnosis or start of primary treatment. More patients received neoadjuvant systemic therapy during 2020 compared with 2019, and this difference was statistically significant ( p = 0.004). There was no difference in the type of surgery (breast-conserving surgery vs. modified radical mastectomy). The results demonstrate that COVID-19 did not appear to negatively impact the diagnosis and treatment of newly diagnosed breast cancer patients. However, this is largely attributable to the significantly less number of patients who registered, for whom the departments were able to maintain timely cancer care despite the difficult pandemic times. Significantly more patients received neoadjuvant systemic therapy in 2020.

A Comparison Between Sequential Conventional and Hypofractionated Boost Following Whole-Breast Radiotherapy: A Propensity Score-Matched Analysis.

BACKGROUND: The majority of local relapses after breast conservation therapy occur in the proximity of the primary lesion. Studies have shown that boost radiotherapy (RT) following conventional whole-breast radiotherapy (WBRT) of 50 Gy in five weeks improves outcomes. Boost RT also increases the risk of moderate skin reactions and fibrosis. The ideal boost RT dose and timing (sequential versus simultaneous) after hypofractionated radiotherapy schedules remain unclear. This retrospective propensity score-matched analysis assessed the outcome of sequential hypofractionated boost compared to conventional fractionated boost. METHODS: The study was approved by the Institutional Review Board of the Regional Cancer Centre, Thiruvananthapuram, India. Patients with stage I-III breast cancer who have received adjuvant radiotherapy with a sequential boost of either hypofractionated RT (8 Gy in three fractions) or conventional fractionated RT (10 Gy in five fractions) after conservative breast surgery were identified from the radiotherapy planning records and included in this study. A 1:1 case matching was performed using a propensity score incorporating four known prognostic factors, namely, clinical and pathological composite stage, tumor grade, tumor biology (based on estrogen and/or progesterone and HER2 neu expression), and boost technique, which may have an impact on acute toxicity to make the two boost groups more homogenous. RESULTS: After propensity score matching (PSM), there were a total of 166 patients, with 83 patients each in both conventional and hypofractionated boost RT groups. The median follow-up period was 30.7 months. At two years, locoregional recurrence-free survival (LRFS) was 98.8% in both groups. Disease-free survival (DFS) at two years for the hypofractionated group and conventional group was 91.5% and 96.3% (hazard ratio (HR): 2.5, 95% confidence interval (CI): 0.664-9.4, p = 0.161), respectively, with no statistically significant difference. Patients with grade 3 tumors who received hypofractionated boost had a statistically significant increased risk of recurrence (DFS: 88.9% versus 100%, HR: 60.559, 95% CI: 0.138-26613.2, p = 0.011). The overall survival (OS) at two years was 100% in both groups. There was no difference in acute skin toxicity between the two groups. CONCLUSION: The present interim analysis shows similar locoregional recurrence-free survival, overall survival, and disease-free survival and acute skin toxicity for hypofractionated boost RT of 8 Gy in three fractions compared to the conventional boost of 10 Gy in five fractions. Hypofractionated boost is a feasible alternative option following hypofractionated whole-breast radiotherapy for women with breast conservation treatment. However, longer follow-up is required before forming definite conclusions.

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.

Ensuring quality in contextualised cancer management guidelines for resource-constraint settings: using a systematic approach.

To address the wide variation in access to cancer care in India requires strengthening of infrastructure, trained oncology workforce, and minimisation of out-of-pocket expenditures. However, even with major investments, it is unlikely to achieve the same level of infrastructure and expertise across the country. Therefore, a resource stratified approach driven by evidence-based and contextualised clinical guidelines is the need of the hour. The National Cancer Grid has been at the forefront of delivery of standardised cancer care through several of its initiatives, including the resource-stratified guidelines. Development of new guidelines is resource and time intensive, which may not be feasible and can delay the implementation. Adaptation of the existing standard guidelines using the transparent and well-documented methodology with involvement of all stakeholders can be one of the most reasonable pathways. However, the adaptation should be done keeping in mind the context, resource availability, budget impact, investment needed for implementation and acceptability by clinicians, patients, policymakers, and other stakeholders. The present paper provides the framework for systematically developing guidelines through adaptation and contextualisation. The process can be used for other health conditions in resource-constraint settings.

Educational Status, Cancer Stage, and Survival in South India: A Population-Based Study.

PURPOSE: Lower socioeconomic status is associated with more advanced cancer at the time of cancer diagnosis. It is unknown whether this leads to inferior survival in low- and middle-income countries. Here, we explore the association between educational level and survival in South India. METHODS: The Trivandrum Cancer Registry (3.3 million population) was used to identify all cases of breast and cervical cancer (women) and oral cavity (OC) and lung cancer (men) diagnosed during 2012-2014. Educational level was classified as illiterate/primary school, middle school, and secondary school and above. Survival was measured from date of diagnosis using the Kaplan-Meier method. Cox proportional hazards regression modeling was used to describe the associations among education, stage of cancer at diagnosis, and survival. RESULTS: The study population included 3,640 patients with breast (n = 1,727), cervical (n = 425), OC (n = 702), and lung (n = 786) cancer. Educational level was 27%, 23%, and 32% for illiterate/primary, middle, and secondary school and above, respectively. The 5-year survival rate for breast cancer was 59%, 68%, and 73% (P = .001); for cervical cancer, 51%, 52%, and 60% (P = .146); and for OC cancer, 42%, 35%, and 48% (P = .012) for illiterate/primary, middle school, and secondary school and above, respectively. The survival gradient across social groups was substantially attenuated when stage was added to the multivariable model. There was no observed difference in survival across educational groups for lung cancer (2%, 4%, and 3%; P = .224). CONCLUSION: Data from this population-based study in South India demonstrate that patients from a lower educational background have inferior survival and that this is at least partially explained by having more advanced disease at the time of diagnosis. Public health efforts are needed to facilitate timely diagnosis and reduce disparities in cancer outcomes.

Does addition of postmastectomy radiotherapy improve outcome of patients with pT1-2, N0 triple negative breast cancer as compared to breast conservation therapy?

BACKGROUND: Triple-negative breast cancers (TNBCs) form a heterogeneous group of cancers typically exhibiting an aggressive behavior resulting in increased risk of locoregional relapse (LRR) and distant metastases. The effect of radiotherapy on LRR risk and overall survival (OS) in women treated with mastectomy alone for early-stage TNBC remains unclear. AIM: The aim of this study is to compare the locoregional recurrence rate, disease-free survival (DFS), and OS following breast conservation therapy (BCT) or modified radical mastectomy (MRM) alone in women with stage I and IIA TNBC and to assess the impact of tumor and treatment-related factors. MATERIALS AND METHODS: Patients with early-stage (pT1-2, N0) TNBC-treated between January 1, 2010, and December 31, 2011, were identified from the hospital-based registry records. The mean age was 48 years. Forty-nine patients underwent BCT, and 121 underwent MRM. The majority of the patients in both groups had T2 and grade 3 disease. None of the patients had margin positive status after surgery. Five patients had lymphovascular invasion (LVI). RESULTS: At a median follow-up of 50 months (range: 4-83 months), there was no locoregional recurrence (LRR) in either arm. Eight patients relapsed, six developed distant metastases, and one patient each had a new primary in the contralateral breast and ovary. Two patients died of disseminated cancer, one each in the BCT and MRM groups. The five-year DFS was 95.8% and 91.1% for the BCT group and MRM group, respectively, (P = 0.83). The corresponding 5-year OS was 98% and 97.5% (P = 0.527). There was no statistically significant difference in outcome based on age, grade, LVI, or margin status between both groups. CONCLUSION: This retrospective analysis identified no statistically significant difference in outcome regarding LRR, DFS, or OS in patients treated without adjuvant radiation for women with pT1-T2N0 TNBC who underwent MRM in comparison to BCT.

Sociodemographic Factors and Stage of Cancer at Diagnosis: A Population-Based Study in South India.

PURPOSE: Lower socioeconomic status is associated with inferior cancer survival in high-income countries, but whether this applies to low- and middle-income countries is not well described. Here, we use a population-based cancer registry to explore the association between educational level and stage of cancer at diagnosis in South India. METHODS: We used the Trivandrum District population-based cancer registry to identify all cases of breast and cervical cancer (women) and oral cavity (OC) and lung cancer (men) who were diagnosed from 2012 to 2014. Educational status-classified as illiterate/primary school, middle school, or secondary school or higher-was the primary exposure of interest. Primary outcome was the proportion of patients with advanced stage disease at diagnosis defined as stage III and IV (breast, cervix, or OC) or regional/metastatic (lung). RESULTS: The study population included 4,547 patients with breast (n = 2,283), cervix (n = 481), OC (n = 797), and lung (n = 986) cancer. Educational status was 22%, 19%, and 26% for illiterate/primary, middle, and secondary school or higher, respectively. Educational status was missing for 33% of patients. The proportion of all patients with advanced stage disease was 37% (breast), 39% (cervix), 67% (OC), and 88% (lung). Patients with illiterate/primary school educational status were considerably more likely to have advanced breast cancer (50% v 39% v 36%; P < .001), cervix cancer (46% v 43% v 24%; P = .002), and OC cancer (77% v 76% v 59%; P < .001) compared with patients with higher educational levels. The proportion of patients with advanced lung cancer did not vary across educational levels (89% v 84% v 88%; P = .350). CONCLUSION: A substantial proportion of patients in South India have advanced cancer at the time of diagnosis. This is particularly true among those with the lowest levels of education. Future health awareness and preventive interventions must target less-educated communities to reduce delays in seeking medical care for cancer.

Impact of subventricular zone irradiation on outcome of patients with glioblastoma.

PURPOSE: Glioblastoma (GBM) is characterized by early relapse and mortality. Treatment resistance could be a characteristic exhibited by pro-genitor neoplastic cells that reside in the subventricular zone (SVZ). This retrospective study was conducted to assess the correlation of SVZ doses and survival in patients with GBM. MATERIALS AND METHODS: Forty-seven patients with GBM treated with radiotherapy, concurrent and adjuvant temozolomide therapy, and whose dosimetry data were available were included. The ipsilateral and contralateral SVZs were delineated on co-registered magnetic resonance imaging-computed tomography images as a 5-mm margin along the lateral wall of the lateral ventricles. Median radiotherapy dose prescribed was 59.4 Gy. The mean ipsilateral, contralateral, and bilateral SVZ doses were 56.3 Gy (range 33-63 Gy), 50.4 Gy (range 23-79 Gy), and 52 Gy (28-69 Gy). The progression-free survival (PFS) and overall survival (OS) were calculated from the date of surgery to the date of radiologic and/or clinical progression and death/last follow-up, respectively. Survival probability was estimated using the Kaplan-Meier method. Log-rank test was used to test the significance between groups. Cox proportional hazards analyses were used to identify prognostic factors. RESULTS: At a median follow-up of 19 months, all patients had relapsed. Most recurrences were infield (n = 39). The median PFS and OS were 17 and 19 months, respectively. The PFS and OS at 2 years were 36.2% and 21.3%, respectively. Patients who received ipsilateral SVZ dose of ≥56 Gy appeared to have better but nonsignificant median PFS and OS. Patients receiving contralateral SVZ doses ≥50 Gy showed a similar trend. Only the number of adjuvant temozolomide (≥6 cycles) showed prognostic impact. CONCLUSION: This retrospective study indicated a trend toward improved-albeit nonsignificant-survival with higher dose to the ipsilateral and contralateral SVZs. A well-designed prospective randomized study is required to identify patients who would benefit from intentional SVZ targeting.

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.

Temporal Trends and Future Prediction of Breast Cancer Incidence Across Age Groups in Trivandrum, South India.

BACKGROUND: Increasing breast cancer (BC) incidence rates have been reported from India; causal factors for this increased incidence are not understood and diagnosis is mostly in advanced stages. Trivandrum exhibits the highest BC incidence rates in India. This study aimed to estimate trends in incidence by age from 2005- 2014, to predict rates through 2020 and to assess the stage at diagnosis of BC in Trivandrum. MATERIALS AND METHODS: BC cases were obtained from the Population Based Cancer Registry, Trivandrum. Distribution of stage at diagnosis and incidence rates of BC [Age-specific (ASpR), crude (CR) and age-standardized (ASR)] are described and employed with a joinpoint regression model to estimate average annual percent changes (AAPC) and a Bayesian model to estimate predictive rates. RESULTS: BC accounts for 31% (2681/8737) of all female cancers in Trivandrum. Thirty-five percent (944/2681) are <50 years of age and only 9% present with stage I disease. Average age increased from 53 to 56.4 years (p=0.0001), CR (per 105 women) increased from 39 (ASR: 35.2) to 55.4 (ASR: 43.4), AAPC for CR was 5.0 (p=0.001) and ASR was 3.1 (p=0.001). Rates increased from 50 years. Predicted ASpR is 174 in 50-59 years, 231 in > 60 years and overall CR is 80 (ASR: 57) for 2019- 20. CONCLUSIONS: BC, mostly diagnosed in advanced stages, is rising rapidly in South India with large increases likely in the future; particularly among post-menopausal women. This increase might be due to aging and/or changes in lifestyle factors. Reasons for the increased incidence and late stage diagnosis need to be studied.

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.

Determinants of participation in a breast cancer screening trial in trivandrum district, India.

BACKGROUND: Conspicuous differences in participation rates for breast self-examination (BSE), clinical breast examination (CBE), and referral for further investigations have been observed indicating involvement of a number of different factors. This study analysed determinants for participation in different levels of the breast cancer screening process in Indian females. MATERIALS AND METHODS: An intervention group of 52,011 women was interviewed in a breast cancer screening trial in Trivandrum district, India. In order to assess demographic, socio-economic, reproductive, and cancer-related determinants of participation in BSE, CBE, and referral, uni- and multi-variate logistic regression was employed. RESULTS: Of the interviewed women, 23.2% reported practicing BSE, 96.8% had attended CBE, and 49.1% of 2,880 screen-positives attended referral. Results showed an influence of various determinants on participation; women who were currently not married or who had no family history of cancer were significantly less likely to attend the screening process at any level. CONCLUSIONS: Increasing awareness about breast cancer, early detection methods, and the advantages of early diagnoses among women, and their families, as well as health care workers offering social support, could help to increase participation over the entire screening process in India.

Clinical breast examination: preliminary results from a cluster randomized controlled trial in India.

A cluster randomized controlled trial was initiated in the Trivandrum district (Kerala, India) on January 1, 2006, to evaluate whether three rounds of triennial clinical breast examination (CBE) can reduce the incidence rate of advanced disease incidence and breast cancer mortality. A total of 275 clusters that included 115,652 healthy women, aged 30-69 years, were randomly allocated to intervention (CBE; 133 clusters; 55,844 women) or control (no screening; 142 clusters; 59,808 women) groups. Performance characteristics (sensitivity, specificity, false-positive rate, and positive predictive value) of CBE were evaluated. An intention-to-treat analysis was performed for comparison of incidence rates between the intervention and control groups. Preliminary results for incidence are based on follow-up until May 31, 2009, when the first round of screening was completed. Of the 50,366 women who underwent CBE, 30 breast cancers were detected among 2880 women with suspicious findings in CBE screening that warranted further investigations. Sensitivity, specificity, false-positive rate, and positive predictive value of CBE were 51.7% (95% confidence interval [CI] = 38.2% to 65.0%), 94.3% (95% CI = 94.1% to 94.5%), 5.7% (95% CI = 5.5% to 5.9%), and 1.0% (95% CI = 0.7% to 1.5%), respectively. The age-standardized incidence rates for early-stage (stage IIA or lower) breast cancer were 18.8 and 8.1 per 100,000 women and for advanced-stage (stage IIB or higher) breast cancer were 19.6 and 21.7 per 100,000 women, in the intervention and control groups, respectively.

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.

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.

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.

Role of xenobiotic metabolizing gene polymorphisms in breast cancer susceptibility and treatment outcome.

Metabolic activation and inactivation of potential genotoxic agents occur by Phase I and Phase II enzymes in multiple interactions. An expanding body of literature demonstrates that ethnic differences in breast cancer incidence may be partly caused by host genetic factors particularly genetic polymorphisms of these carcinogen-metabolizing enzymes. The present case-control study aimed at identification of such low penetrance breast cancer susceptibility genes in 224 Indian women and to investigate the potential effects of their polymorphisms on sporadic breast cancer risk. The main objective of the study was to evaluate the effects of genetic polymorphisms of the xenobiotic metabolizing genes CYP1A1, GSTM1 and GSTT1 on breast cancer risk by PCR-RFLP and DNA sequencing. Our results showed a significant association between CYP1A1 m1, m2 polymorphisms and breast cancer risk; however there was a lack of association between GSTM1 null deletion and breast cancer. The associations of CYP1A1, GSTM1 and GSTT1 genotypes with breast cancer risk were more pronounced among the pre-menopausal patients. Combined genotype analysis revealed the CYP1A1 m2 ValVal-GSTM1 homozygous null deletion genotype combinations to be associated with the highest risk of breast cancer (OR=10.3, 95% CI=1.2-86.1). Correlations with clinicopathological factors and treatment outcome were also analyzed for predicting disease free survival by univariate and multivariate analysis. Significant differences in disease free survival between the wild and polymorphic genotypes were observed only for CYP1A1 m2, GSTT1 genotypes. Our results based on the analysis of functionally relevant polymorphisms in these low penetrance genes may provide a better model that would exhibit additive effects on individual susceptibility to breast cancer. Such genotype analysis resulting in a high-risk profile holds considerable promise for individualizing screening and therapeutic intervention in breast cancer. Hence, the present study may provide strong supportive evidence for genetic interactions in the etiology of breast cancer.

Polymorphisms in DNA repair gene XRCC1 and increased genetic susceptibility to breast cancer.

X-ray repair cross-complementing 1 (XRCC1) gene encodes for a scaffolding protein, which plays an important role in base excision DNA repair by bringing together DNA polymerase beta, DNA ligase III and poly(ADP-Ribose) polymerase (PARP) at the site of DNA damage. Three polymorphisms of the XRCC1 gene at codons 194, 280 and 399 leading to amino acid changes at evolutionary conserved regions are found to alter the efficiency of the resulting protein and may therefore constitute potential breast cancer risk. In the present study we sought to determine whether these genetic variants of the XRCC1 gene was associated with any increased risk of breast cancer among the South Indian women in a hospital based case control study using PCR-RFLP and DNA sequencing techniques. Our data showed a positive association between the polymorphisms of codons 194 (OR = 1.98, 95% CI = 1.13-3.48 for Trp allele) and 399 (OR = 2.14, 95% CI = 1.29-3.58 for Gln allele) and breast cancer risk. However, XRCC1 codon 280 genotype analysis showed no evidence for an association with increased risk of breast cancer. A combined analysis of the effect of XRCC1 codon 194 and 399 revealed the highest risk (OR = 3.64, 95% CI = 1.57-8.46) for carriers of the polymorphic alleles in both these codons. In conclusion, the present study suggested involvement of XRCC1 codon 194 and 399 polymorphisms in the genetic predisposition to breast cancer among South Indian women. Our preliminary results based on the analysis of functionally relevant polymorphisms in XRCC1 low penetrance gene may provide a better model that would exhibit additive effects on individual susceptibility to breast cancer.

CYP17 and SULT1A1 gene polymorphisms in Indian breast cancer.

BACKGROUND: Breast cancer is the most common cancer among women worldwide. Life-time exposure to steroid hormones, especially estrogen, is a major risk factor for breast cancer. Functional polymorphisms in genes encoding steroid metabolizing enzymes may thus be important as biomarkers of individual susceptibility to breast cancer. The CYP17 and SULT1A1 genes encode for two enzymes involved in hormone biosynthesis and metabolism. Single nucleotide polymorphisms of these genes may result in inter-individual variability in steroid hormone biosynthesis and metabolism thus influence the development of breast cancer. METHODS: We tested this hypothesis by conducting a case - control study on a group of 140 breast cancer cases and 140 healthy age-matched controls. Analysis of CYP17 and SULT1A1 genotypes were done by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). RESULTS: The genetic polymorphisms of the estrogen-related genes SULT1A1(OR=2.5, 95% CI=1.28-4.98) and CYP17 (OR=4.1, 95= CI=1.78-9.63) were associated with an increased risk of breast cancer among postmenopausal women. Our data also showed evidence for the genetic regulation of serum 17 beta estradiol (E2) levels as measured by ELISA among the premenopausal women with a significant increase in the serum E2 level for the CYP17 A2 variants. CONCLUSION: These results suggest that both CYP17 and SULT1A1 genotypes could be important determinants of breast cancer risk in Indian women and may help in early identification of high risk subjects. Such genotype analysis resulting in a high-risk profile holds considerable promise for individualizing screening, diagnosis and therapeutic intervention in breast cancer.