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.

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.

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.

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.

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.

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.