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Lahore, Pakistan

Khokher S.,Services Hospital | Qureshi M.U.,Nauman Associates | Mahmood S.,University of Punjab | Sadiq S.,INMOL Hospital
Asian Pacific Journal of Cancer Prevention

Background: Breast cancer is the most frequent cancer of women in Pakistan with the majority presenting with stage III or IV lesionsat initial diagnosis. Patient and health system related factors are well known determinants of delay in presentation and diagnosis. Additionally, breast cancer being a heterogeneous disease, the various molecular subtypes featuring different aggressiveness also need to be considered. The present study evaluated the association of stage at initial diagnosis of breast cancer with these two factors in local women at a tertiary level health care facility in Lahore, Pakistan. Materials and Methods: Patient and tumor features were recorded separately during diagnostic workup in Breast Clinics at INMOL and at Services Hospital, Lahore. Data were entered in MS Excel and analyzed by descriptive statistics and Chi-Square test. Results: Among the 261 patients, 64% were staged as late breast cancer (LBC), the mean age was 46.8 with standard deviation of 13 years. Some 92% had invasive ductal carcinoma (IDC), 61% had luminal types (LT) of non-aggressive tumor while 39% had the non-luminal types (NLT) of of HER2-enriched or basal aggressive tumors. While 70% of patients presented within one year of symptomatic disease (early report group "ERG"), 30% reported after a mean delay of 4 years with a standard deviation of 3.75 years. The stage distribution among ERG patients was not statistically different from those reporting late (P=0.123). Statistically larger proportion of patients with NLT presented as LBC as compared to the LT (P =0.034). Among the ERG, statistically different stage distribution of disease was observed for the NLT versus LT (P=0.047). Among those presenting late, this difference was insignificant (P=0.416). Conclusions: Breast cancer is a distinct disease in Pakistan with a high frequency of aggressive molecular types affecting younger women, with the majority presenting as LBC. Association of NLT with higher stage at diagnosis is statistically significant whereas time delay in diagnosis is not. Further research is required to define the risk profile and features in local patients. The burden of LBC can be reduced by promoting breast health awareness and by establishing easily accessible dedicated breast care set ups in the hospitals. Source

Khokher S.,INMOL Hospital | Qureshi M.U.,Nauman Associates | Chaudhry N.A.,University of Health Sciences, Lahore
Asian Pacific Journal of Cancer Prevention

When patients with advanced breast cancer (ABC) are treated with neoadjuvant chemotherapy (NACT), efficacy is monitored by the extent of tumor shrinkage. Since their publication in 1981, World Health Organization (WHO) guidelines have been widely practiced in clinical trials and oncologic practice, for standardized tumor response evaluation. With advances in cancer treatment and tumor imaging, a simpler criterion based on onedimensional rather than bi-dimensional (WHO) tumor measurement, named Response Evaluation Criteria in Solid Tumors (RECIST) was introduced in 2000. Both approaches have four response categories: complete response, partial response, stable disease and progressive disease (PD). Bi-dimensional measurement data of 151 patients with ABC were analysed with WHO and RECIST criteria to compare their response categories and inter criteria reproducibility by Kappa statistics. There was 94% concordance and 9/151 patients were recategorized with RECIST including 6/12 PD cases. RECIST therefore under-estimates and delays diagnosis of PD. This is undesirable because it may delay or negate switch over to alternate therapy. Analysis was repeated with a new criteria named RECIST-Breast (RECIST-B), with a lower threshold for PD (≥10% rather than ≥20% increase of RECIST). This showed higher concordance of 97% with WHO criteria and re-categorization of only 4/151 patients (1/12 PD cases). RECIST-B criteria therefore have advantages of both ease of measurement and calculations combined with excellent concordance with WHO criteria, providing a practical clinical tool for response evaluation and offering good comparison with past and current clinical trials of NACT using WHO guidelines. Source

Khokher S.,INMOL Hospital | Mahmood S.,University of Health Sciences, Lahore | Qureshi M.U.,University of Health Sciences, Lahore | Khan S.A.,University of Health Sciences, Lahore | Chaudhry N.A.,University of Health Sciences, Lahore
Asian Pacific Journal of Cancer Prevention

Neoadjuvant chemotherapy (NACT) is well established as the standard of care and initial management of choice for patients with advanced breast cancer (ABC). The response is however not uniform. The present study was an endeavor to develop a clinically applicable tool based on the available clinico-pathological data in the routine clinical setting to predict response to chemotherapy in breast cancer in a developing country. From 1st June 2005 to 30th June 2007, 149 patients registered at INMOL hospital with ABC at initial diagnosis having tumor size 5 cm or more and treated with FAC as NACT were prospectively included in the study to analyze association of response after first cycle of chemotherapy (initial clinical response) with that after the third cycle. Tumor measurements were done at base line (before starting chemotherapy), three weeks after the first course of chemotherapy and three weeks after the third course. Percentage change was calculated for the latter two stages. Clinical response was assessed according to WHO/UICC criteria. Pathological complete response (pCR) was based on the histopathology of the operative specimen after NACT. 67.1% patients (cCR 7.4%+cPR 59.7%) responded to chemotherapy while 32.9% (cSD 23.5%+cPD 9.4%) did not. pCR rate was 4%. No patient had initial clinical complete response while 23% had icPR, 74% had icSD and 3% had icPD. All patients with icPR responded to NACT (cCR 29%+cPR 71%) while 60% of icSD responded to chemotherapy (cCR 1%+cPR 59%) and 40% of icSD failed to respond (cSD 31%+cPD 9%). All patients with icPD developed cPD. The high sensitivity of initial clinical response for prediction of cCR and 100% specificity of icPD for prediction of cPD favors its incorporation in clinical practice, as an early predictor of response to NACT in ABC patients. Source

Khokher S.,INMOL Hospital | Mahmood S.,Health Science University | Khan S.A.,Post Graduate Medical Institute Lahore
Asian Pacific Journal of Cancer Prevention

A large proportion of women present with advanced breast cancer in the developing countries with limited resources. Many of these patients have ulcerated, bleeding lesions or visually obvious masses in the breast. Neoadjuvant chemotherapy is well established as the standard of care and initial management of choice for these patients. Tumor shrinkage achieved with neoadjuvant chemotherapy has the advantage of converting an inoperable disease to an operable condition, with the option of breast conservation surgery where mastectomy is the only initial option for loco-regional control. Neoadjuvant chemotherapy also provides the earliest possible treatment of micrometastases and thus improves survival. In the present study, 165 advanced breast cancer female patients registered at the Institute of Nuclear Medicine and Oncology, Lahore, Pakistan, between 1st July 2005 and 30th June 2007 were evaluated for response to neoadjuvant chemotherapy. Tumor measurements were made and recorded prior to the first cycle of chemotherapy and 3 weeks after the third cycle. A clinical complete response was seen in 7.3%, a partial response in 60%, stable disease in 24% and progressive disease in 9%. A complete pathological response was only seen in 3.6% of evaluable patients. We conclude that breast cancer in patients presenting for neoadjuvant chemotherapy at our facility is more aggressive, generally presents as more advanced and bulky local disease, affects a younger population and features a low and unpredictable response to neoadjuvant chemotherapy. Source

Khokher S.,INMOL Hospital | Qureshi M.U.,Nauman Associates | Riaz M.,Medical Physics, Inc. | Akhtar N.,Medical Physics, Inc. | Saleem A.,Central Park Medical College
Asian Pacific Journal of Cancer Prevention

Breast cancer is the most frequent cancer of women worldwide, with considerable geographic and racial/ethnic variation. Data are generally derived from population based cancer registries in the developed countries but hospital data are the most reliable source in the developing countries. Ten years data from 1st Jan 2000 to 31st Dec 2009 of a cancer hospital in Pakistan were here analyzed by descriptive statistics to evaluate the clinicopathologic profile of local breast cancer patients. Among 28,740 cancer patients, 6,718 were registered as breast cancer. The female to male ratio was 100:2. Breast cancer accounted for 23% of all and 41% of female cancers. Some 46% were residents of Lahore, with a mean age of 47±12 years. Less than 1% were at Stage 0 and 10%, 32%, 35% and 23% were at Stage I, II, III and IV respectively. Histopathology was unknown in 4% while 91%, 2% and 1% had invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC) and mucinous carcinoma respectively. Rare carcinomas accounted for the rest. Tumor grade 1, 2 and 3 was 11%, 55% and 34% among the known. Profile of breast cancer patients in Pakistan follows a pattern similar to that of other developing countries with earlier peak age and advanced disease stage at presentation. The male breast cancer accounts for higher proportion in the local population. Local women have higher frequency of IDC and lower frequency of ILC and DCIS, owing probably to a different risk profile. Use of hospital information systems and establishment of population based cancer registry is required to have accurate and detailed local data. Promotion of breast health awareness and better health care system is required to decrease the burden of advanced disease. Source

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