Validation of EORTC quality-of-life questionnaire in Indian women with operable breast cancer.

BACKGROUND: The European Organization for Research and Treatment of Cancer (EORTC) module QLQ-C30 and the breast cancer-specific module BR-23 have been validated worldwide to assess the quality of life (QOL) in women with breast cancer. No such study has been published on Indian women using EORTC questionnaires. METHODS: QOL was assessed in relation to surgery, adjuvant chemotherapy, radiation therapy and hormone therapy in 299 Indian women with operable breast cancer (OBC) at the Breast Unit of Tata Memorial Hospital (TMH), Mumbai, from October 1998 to September 2001. The QLQ-C30 module was used to assess physical health, emotional, cognitive and social functioning, and the BR-23 module to assess breast cancer treatment-related symptoms. Assessment was done at 3 visits: visit 1 (after surgery); visit 2 (during adjuvant therapy) and visit 3 (on completion of adjuvant therapy). RESULTS: Of the 299 women at first visit, 274 (91.6%) completed the visit 2 questionnaire and 239 (80%) completed the visit 3 questionnaire. Only those women who filled the questionnaires at all 3 visits were included as 'valid visits' for analysis (193 of 299; 64.5%). The reliability and validity of the English and translated versions of the questionnaires were tested by Cronbach alpha (0.61-0.96) and item-scale correlation (0.63-0.93). Women with breast conservation treatment had a superior body image as compared to those with mastectomy (p <0.001). Physical, emotional and cognitive functions were not related to the type of surgery. Global QOL, physical, sexual and role functioning were found to deteriorate with chemotherapy (p < or = 0.01). Radiotherapy had only local adverse effects (p < 0.001 ), while hormone therapy had no adverse impact on QOL. CONCLUSION: QLQ-C30 and BR-23 questionnaires can be used reliably to assess QOL in Indian patients. The translated versions were found to be valid for further use in clinical trials on Indian women with breast cancer.

Timing of surgery during the menstrual cycle and prognosis of breast cancer.

There are conflicting reports on the differential effect of surgery performed during the two phases of the menstrual cycle, namely, follicular and luteal, and prognosis of operable breast cancer. A statistical meta-analysis of the published evidence suggests a modest survival benefit of 15+/-4% when the operation is performed during the luteal phase. Further research in this area might provide a novel avenue to understand the natural history of breast cancer. A spin off from these studies might be the understanding of the importance of events that occur at the time of surgery in determining long term prognosis.

Analysis of BRCA1 involvement in breast cancer in Indian women.

The involvement of the familial breast-ovarian cancer gene (BRCA1) in the molecular pathogenesis of breast cancer among Indian women is unknown. We have used a set of microsatellite polymorphisms to examine the frequency of allele loss at the BRCA1 region on chromosome 17q21, in a panel of 80 human breast tumours. Tumour and blood leukocyte/normal tissue DNA from a series of 80 patients with primary breast cancer was screened by PCR-amplified microsatellite length polymorphisms to detect deletions at three polymorphic BRCA1 loci. PCR-allelotype was valuable in examining allele losses from archival and small tumour samples. Loss of alleles at BRCA1 in the patient set, confirmed a noteworthy role of this gene in the molecular patho-genesis of breast cancer and was in accordance with its well-documented tumour suppressive function.

Prognostic significance of DNA index by flowcytometry in acute lymphoblastic leukaemia.

DNA index (DI) is considered an important prognostic factor in acute lymphoblastic leukaemia (ALL). We undertook this study to correlate DI with other presenting features and response to therapy. Of the 30 patients of ALL treated at our hospital and entered in this study, 15 were put on the aggressive MCP (multi center protocol) 841 protocol and equal number on the Alternate protocol. Eighteen achieved complete remission (13/15 on the former protocol and 5/15 on the later). DI was less than 0.8 in 8 (27%) patients, between 0.8 and 1.2 in 18 (60%) and more than 1.2 in 4 patients (13%). These figures are different from those reported in Caucasians. On multivariate regression analysis, the DI significantly correlated with percentage of blasts in peripheral blood (P = 0.0035). There was no correlation with outcome or response to treatment.

DNA analysis of breast cancer by flow cytometry & correlation with other prognostic parameters.

Flow cytometric estimation of DNA content (ploidy and S-phase fraction--SpF) was done on breast cancer tissues from 171 patients. Twenty eight per cent of the tumours were diploid and 72 per cent were aneuploid. SpF was measurable in 82 DNA histograms; of these 22.4 per cent had SpF less than 10 per cent, 34.1 per cent had SpF between 10-20 and 43.5 per cent had SpF greater than 20 per cent. The mean SpF of the measurable histograms was 19.01 per cent with a range 1.78 to 45.19 per cent. A significant correlation between DNA ploidy and SpF was observed (P less than 0.01). Eighty nine per cent of diploid tumours had SpF less than 10 per cent and 73 per cent of aneuploid tumours had SpF greater than 20 per cent. A significant correlation was also found between ploidy and SpF and oestrogen receptor (ER) status of the tumours (P less than 0.05) and between SpF and progesterone receptor (PgR) status of the tumours (P less than 0.05), but not between ploidy and PgR status of the tumours. A significant direct correlation was observed between SpF and tumour grade (P less than 0.05), but not between ploidy and tumour grade. No correlation was observed between DNA ploidy and SpF and tumour type, tumour size, axillary lymph node involvement, age and menopausal status of the patients. Although the incidence of breast cancer is one-third of that reported in the Western countries, there is apparently no biological difference between the various parameters studied.

Estrogen & progesterone receptors measurement in breast cancer with enzyme-immunoassay & correlation with other prognostic factors.

Estrogen and progesterone receptor (ER and PgR) estimation was carried out by an enzyme-immunoassay by a 'sandwich' technique using two different monoclonal antibodies against each receptor on 508 consecutive breast cancer samples. 43.9 per cent of the tumours were ER+ve and 26.6 per cent were PgR+ve; 23.8 per cent were both ER and PgR+ve, 53.3 per cent were both ER and PgR-ve, 20.0 per cent were ER+ve PgR-ve and 2.8 per cent were ER-ve PgR+ve. Both ER and PgR positivity was associated with increasing age, and this was seen within both pre and post-menopausal subgroups. Grades I and II tumours were more often ER and PgR+ve compared with grade III tumours, indicating that receptor positivity is a marker of a more well differentiated tumour phenotype. Receptor positivity was higher in primary tumours compared to that in metastatic tissues. The proportion of tumours that was ER+ve was found to vary among the four major religious communities, viz., Hindu, Muslim, Christian and Parsi, and this variation was significant in the overall analysis (P less than 0.01). The Christians had the highest rate of ER+ve tumours while the Muslims had the lowest rate. No correlation was observed between ER and PgR status and axillary nodal involvement or tumour size, suggesting that ER and PgR are independent prognostic factors in breast cancer. We found the EIA method to be an easy and rapid technique for ER and PgR analysis and which requires a small amount of tissue and does not involve the use of radioisotopes.

Differences in oestrogen receptor status and histological grade of breast cancer in different religious communities in Bombay.

The various religious communities in India viz.Hindu, Muslim, Christian, Parsi have different breast cancer incidence rate. It is not known whether there might also exist differences in biological properties of breast cancer between these communities. To investigate this possibility we have studied the distribution of oestrogen receptor (ER) status and histological grade of tumour in these four communities. Significant differences were observed in the overall distribution of ER positivity and histological grade between the communities P less than for both parameters). Christians had the highest incidence of ER +ve (65.2%) and grade I + II tumours (16.0%), while Muslims had the lowest incidence of ER +ve (35.8%) and Grade I + II tumours (4.7%). In general, we found a significant positive relationship between ER status and age of the patient (p less than 0.0.1). The mean age of the christians was slightly but significantly higher than that of the Hindus and Muslim. The difference ER positivity between the communities might, therefore, be partly (but probably not wholly) explained by difference in age of the patients. However, the difference with respect to grade of tumour cannot be explained as a function of age since no significant association was found between grade of the tumour and age of the patient. Further investigation with respect to difference in the biology of the breast cancer between the communities are warranted.

A comparative study of dextran coated charcoal (DCC) and enzyme immunoassay (EIA) methods for oestrogen receptor (ER) estimation in breast cancer.

Oestrogen receptor (ER) concentrations were measured in 100 breast cancer cytosols using both the dextran coated charcoal assay (DCC with 6--point scatchard plot) and a newly developed enzyme linked immunoassay (EIA) using a monoclonal antibody against ER. The efficiency of the two methods was compared. A highly significant correlation was observed between the ER levels determined by DCC and EIA methods (r = 0.94, p less than 0.001). The mean ER-EIA value (43.25 +/- 74.77) was, however, significantly higher than the mean ER-DCC value (18.00 + 37.27) (p less than 0.001); in both pre- menopausal (p less than 0.001) and post-menopausal (p less than 0.001) groups. Using a cut-off point at 10 fmo/mg protein for ER-EIA and 3 fmol/mg protein for ER-DCC/to distinguish ER +ve and -ve tumours, a 97% concordance between the two assays was achieved. The EIA method appears to be preferable to the DCC method because it is easy to perform, rapid, requires less tissue and does not involve the use of radioactive substances.

Clinico-pathological features and prognosis of breast cancer in different religious communities in India.

A study of clinical and pathological features, patterns of relapse and prognosis of breast cancer in various religious communities--viz. Hindu, Muslim, Christian and Parsi--was undertaken among 4377 evaluable cases treated at Tata Memorial Hospital between 1965 and 1982. Of these 82.4 per cent were Hindus, 7.3 per cent Muslims, 7.4 percent Christians and 2.7 percent Parsis. The mean age at diagnosis was 55 years for Parsis which was 7 to 8 years older than that for the other communities. There were no remarkable differences in histological tumour type or grade; except that parsis had higher incidence of uncommon histological types, such as dust carcinoma in situ and colloid carcinoma, and had a slightly more favourable grade distribution. When classified according to the TNM system (UICC 1978), the Parsis had the most favourable stage at presentation followed by Christians, Hindus and Muslims in that order. This trend was highly statistically significant (p less than 0.001). Despite this significant differences between stage of disease at diagnosis, no differences in the overall 5-year survival was observed between the communities. This remained true even after matching for disease stage and menopausal status. Even the Parsis, in whom the disease was detected relatively early, failed to register a survival advantage. Much work need to be done with regard to early detection of Breast Cancer in India.