An institutional review of tumour biology of breast cancer in young Nepalese women

Introduction: Breast cancers in less than 40 years of age group usually present with aggressive biology and has poor prognosis. The aim of this study was to see clinic-pathological and hormone receptors of breast cancers in young women and compare with less than 40 year age group. Methods: Prospective analysis of 97 breast cancer in patients less than 40 years out of total 373 patients (26%) over a period of 8 years (2007 Jan to 2014 Dec) was carried out at the Department of Surgery, Tribhuvan University Teaching Hospital, Kathmandu, Nepal. Result: Among the young women diagnosed with breast cancer, the mean age was 34.5±6.2 years. Mean tumour size was larger in younger women (5±2.5 vs 4.5±2.4 cm). Locally advanced disease was higher in younger patients (55% vs 47%). Lymphatic and vascular invasions were higher (63% vs 35% and 40% vs 25%). Grade II and III tumours was higher (56% vs 25%). ER, PR and HER2 positivity was detected in 46.9%, 48.9% and 28.9% respectively. Significant lower ER or PR expression (34.5% vs 54%) was seen in younger women, p=.002.Triple negative tumours (ER -ve, PR -ve and HER2 -ve) was proportionately higher in younger patients (23% vs 13.7%, p=.043). Conclusion: Young Nepali women presents one quarter of all female breast cancers, more frequently locally advanced with aggressive tumour biology like ER/PR negative and triple negative breast cancers.


Introduction
Breast cancer is the most common cancer in women comprising 23% of all the cancer in women and is the leading cause of cancer death in women, with an estimated 1.15 million new cases per year 1 .Breast cancer is a heterogeneous group of tumour with variable morphology, behaviour, response to therapy, and molecular profile.Tumour with similar clinic-pathological presentations have different behaviours.Young women develop more aggressive subtypes of breast cancer 2 .Young age remains an independent risk factor for poor survival in breast cancer.Breast cancer incidence rate in young is low compared to elder population but it has unique biological features that are not observed in elder population 3 .Young breast cancer represents 5-7% of all breast cancer in developed world whereas same incidence rate in developing countries is around 25% 4 .Young patients tend to have more ERnegative, higher grade, and have increased, Ki-67, and p53 with same HER 2 neu expression 5 .Diagnostic delay often occurs in young patient resulting advanced disease in initial presentation because of younger women themselves unaware of breast cancer and by physicians who are less suspicious of this disease in young patients 6 .
This study has been undertaken to look into incidence and tumour biology of breast cancer represented by the expression of hormone receptor status in young patient age less than 40 years and compare with older population in the same time frame.

Methods
This was a prospective study conducted in the Department of Surgery in Tribhuvan University Teaching Hospital, Maharajgunj Kathmandu Nepal from January 2007 to December 2013.Consecutive breast cancer patients who were operated in the institute were included in the study.Early Breast cancer patients were taken for upfront surgery either Modified Radical Mastectomy or Breast Conserving Surgery if qualified.(Figure 1) Locally advanced breast cancer patients were considered for neo-adjuvant chemotherapy and subsequently taken for surgery.Various parameters like demography, clinical history, tumour characteristics, treatment, histopathology and immunohistochemistry for hormone receptor: ER, PR, HER2 neu status were analysed.These parameters were analysed and compared between two age groups age less than 40 years considered as young breast cancer patients and that more than 40 years age group were considered as elder breast cancer patients.Clinic-pathological characteristics and tumour biology as expressed by hormone receptor status were analysed among these two groups.

Figure 1: Modified Radical Mastectomy Specimen
The categorical data was analysed using Chi square/ Fisher exact test wherever applicable.The ordinal data like tumour grading was analysed by applying Chi square linear trend test.The student's t test was applied to compare continuous data in two groups.Computer software (SPSS/PC 20 version) was used to analyse the data..However, this study showed no difference in expression of HER2neu receptor between young breast cancer patients and old breast cancer patients.

Comparative
Triple negative breast cancer (TNBC) associated with distinct clinical and pathologic characteristics such as diagnosis at younger age and with higher grade 16 .Lack of established receptors reduces the therapeutic options and remains a challenge to treat by targeted therapy 17 .Patients with BRCA1 mutation tend to have ER, PR and HER 2 neu receptors negative and presents with higher grade 18 .In this study, there is statistically significant high percentage of triple negative breast cancer in less than 40 years age group compared to more than 40 years age group patients.
Breast tumour bi ology is more aggressive and is associated with an unfavourable prognosis in younger women 19 .In this study, young breast cancer patients was found to have adverse tumour biology with more patients with TNBC, more patients with ER negative tumour,more of lymph node positivity and with higher grade compared to old breast cancer patients.

Conclusion
Young Nepalese women present one quarter of all female breast cancers, more frequently locally advanced with aggressive tumour biology like ER/PR negative and triple negative breast cancers.

Table 1 )
analysis of patient demography, tumour characteristics and tumour biology were done between age less than 40 years and age more than 40 years.Total number breast cancer patients were 373 among them 97 (26%) were from less than 40 years age whereas 276 (74%) were from more than 40 years age group.Earliest age presenting with breast cancer is 22 years.Mean age at presentation in less than 40 years age group is 34.5±6.2 years and that in more than 40 years age group is 54.1±9.9 years.Higher percentage of breast cancer was from age less than 40 years from Tibeto-Burman descent compared to urban residents.(Table.

Table 2 : Comparison of ER PR HER 2 neu expression between two groups
10ung breast cancer comprises of 26% of total breast cancer patients in our study.Younger patients presented late mean duration of symptoms 7.6±6.5 months versus 6.5±5.7 in more than 40 years age group which was significant statistically.The diagnostic delay in young patients is usually due to patients themselves, as they are often less concerned about and aware of breast cancer, and by physicians, who have less suspicion of this disease in younger women9.Palpable lymph nodes present in axillae breast cancer represent aggressive and likely to have systemic disease compared to non-palpable axillary lymph nodes10.Young breast cancer patients had axillary lymph nodes palpable in 73% of the patients compared to 59% in breast cancer patients in age more than 40 years age group.Young breast cancer patients were more of locally