|Year : 2019 | Volume
| Issue : 2 | Page : 71-75
Study of evolving trends in the clinicopathological profile of breast cancer patients attending a tertiary cancer center
Deep Sikha Das, Indibor Singh Yengkhom, Vimal Sekar, Sunita Akoijam, Ambika Devi Adhikarimayum, James Lalzuitluanga Chongthu
Department of Radiotherapy, Regional Institute of Medical Sciences, Lamphelpat, Imphal, Manipur, India
|Date of Submission||09-Apr-2019|
|Date of Decision||02-Nov-2019|
|Date of Acceptance||25-Nov-2019|
|Date of Web Publication||11-Feb-2020|
Deep Sikha Das
Department of Radiotherapy, Regional Institute of Medical Sciences, Lamphelpat, Imphal - 795 004, Manipur
Source of Support: None, Conflict of Interest: None
Background: Breast cancer is by far the most frequent cancer in the women of Northeast India, with the possibility of 1 in 83 females developing breast cancer in their lifetime. Manipur presents a similar picture with breast cancer comprising 15.3% of female cancers. With westernization of lifestyle, there has been an increase in the prevalence of risk factors. The present study tries to evaluate the changing trends in the demographic, clinical, and pathological profile of the breast cancer patients presenting to a tertiary cancer center in Northeast India within a time frame of 10 years' gap.
Materials and Methods: In this descriptive, retrospective study, the records of histologically confirmed cases of breast cancer managed at the institute a decade apart were analyzed with respect to the various risk factors, stage, histological features, and receptor status. Changes in the trends were recorded.
Results: The mean age at presentation was found to be younger in 2015–2017 compared to 2002–2004 (P < 0.05). More premenopausal women were diagnosed with breast cancer in 2015–2017 as compared to 2002–2004 (P < 0.005). When age at first childbirth was compared, there was significantly advanced age in 2015–2017. Body mass index was significantly higher in 2015–2017 group. When change in receptor status was evaluated, there was a decrease in cases of estrogen receptor/progesterone receptor positivity and increase in triple-negative cases in 2015–2017, which was statistically significant (P < 0.05).
Conclusion: Within an interval of a decade, there has been a significant change in the clinicopathological profile of the breast cancer patients presenting to the institute. More aggressive patterns of disease have become more common with early age of presentation and aggressive biological behavior of receptor-negative tumors. Thus, we need to have a relook at the strategy to manage breast cancer in the coming future.
Keywords: Breast cancer, changing trends, patient profile
|How to cite this article:|
Das DS, Yengkhom IS, Sekar V, Akoijam S, Adhikarimayum AD, Chongthu JL. Study of evolving trends in the clinicopathological profile of breast cancer patients attending a tertiary cancer center. J Med Soc 2019;33:71-5
|How to cite this URL:|
Das DS, Yengkhom IS, Sekar V, Akoijam S, Adhikarimayum AD, Chongthu JL. Study of evolving trends in the clinicopathological profile of breast cancer patients attending a tertiary cancer center. J Med Soc [serial online] 2019 [cited 2020 Oct 22];33:71-5. Available from: https://www.jmedsoc.org/text.asp?2019/33/2/71/278107
| Introduction|| |
Breast cancer is the most common female cancer worldwide, representing nearly a quarter of all cancers. The estimated number of incident breast cancer cases in India in 2016 was 118,000 and the prevalent cases were 526,000. Breast cancer is the leading cancer in Indian females, accounting for the largest crude incidence rate and prevalence of any cancer type. Over the last 26-year period, the age standardized incidence rate of breast cancer in females increased by 39.1% from 1990 to 2016, with an increase observed in every state of the country. Breast cancer was the first or second leading cause of cancer deaths among females in 28 Indian states in 2016. Breast cancer projection of India during 2020 is suggested to go as high as 1,797,900 cases, with the relative percentage remaining 10% of all cancers. In Manipur, breast cancer comprises 15.3% of female cancers, thus occupying the top position with probability of 1 in 97 females developing breast cancer.
Although the incidence rate of breast cancer is known to vary from region to region, the common risk factors are early menarche, delayed menopause, null parity, delayed first childbirth, family history of breast cancer, lack of breastfeeding practice, obesity, tobacco and alcohol consumption, and high-fat high-calorie diet. In management of breast cancer, however, clinicopathological parameters such as tumor size, type, grade, and lymph node status are important for classification, treatment, and prognostication.,
The present study is carried out in a state of northeast of India. This region of India is unlike the rest of the country regarding customs, assorted ethnic groups with their typical food habits, lifestyle, and varying types and patterns of tobacco and alcohol use. Moreover, due to its unique and strategic geographic location with age-old history of migrations, it is considered as a genetic pool., The present communication is a study to evaluate the change in trends of various clinicopathological factors and disease and patient profile of breast cancer patients over a decade of time gap. The changing profile mandates a relook at strategy to manage breast cancer as they are both prognostic and predictive factors.
| Materials and Methods|| |
The aims and objectives were to evaluate the patient and disease profile of breast cancer patients presenting in 2002–2004 and 2015–2017 and to evaluate the change in trend with a gap of a decade.
The study comprised 218 biopsy-proven patients of carcinoma breast treated in a tertiary cancer center in a gap of a decade. One group consisted of patients treated from January 2002 to December 2004 (n = 68) and the other group comprised patients treated from January 2015 to December 2017 (n = 150). An approval from the Institutional Ethics Committee was obtained before the study was conducted. Confidentiality of the patient's identity was maintained. A detailed analysis was carried out with respect to various demographic, clinical, and pathological factors, namely, age, locality, family and tobacco history, menopausal status, age at menarche and menopause, parity, age at first child birth, history of breast feeding, body mass index (BMI), stage of disease, histological type, grade, and receptor status of all the patients. All parameters were entered into a computerized database. The changes in parameters related to demographic, clinical, and pathological factors were compared and recorded.
For statistical analysis, data are presented in frequency tables, charts, and mean ± standard deviation. To see the change in trends in various demographic and clinicopathological factors over time, Chi-square trends test with varying degree of freedom for various factors was used to depict the linear trend in proportion. A P < 0.05 was taken as statistically significant. All the statistical analysis was performed using software IBM corps SPSS version 21 (2015).
| Results and Observations|| |
The most common age group in 2002–2004 was 46–55 years while the most common age group in 2015–2017 was 36–45 years [Table 1]. Mean age at presentation was 49.3 ± 4.3 years in 2015–2017 as compared to 44.76 ± 2.1 years in 2002–2004, and this was significantly younger (P = 0.048). Range of age was 28–76 years in 2002–2004 against 30–69 years in 2015–2017. Although there was an increase in the proportion of rural patients seeking medical care in the 2015–2017 group, this trend was not significant. There was increase in proportion of patients giving a positive family history in 2015–2017, but this trend was not significant. There was increase in proportion of patients giving a positive history of tobacco consumption in any form in 2015–2017 against 2002–2004.
More premenopausal women presented with breast cancer in 2015–2017, and this change in trend of presentation was significant (P = 0.035). Mean age at menarche and mean age at menopause showed no significant difference, with 11–12 years and 53–55 years being the most common age group in both decades. Mean BMI of patients increased from 24.13 in 2002–2004 to 26.45 in 2015–2017. Proportion of overweight patients increased significantly over the decade (P < 0.05). There was a decrease in proportion of women breast feeding their babies in 2015–2017 as compared to 2002–2004.
There was increase in the proportion of nulliparous women and women with single child in 2015–2017 group, but this change in trend was not significant [Table 2]. Mean age of first childbirth was 30.6 years ± 2.3 years in 2015–2017 as compared to 26.67 ± 3.1 years in 2002–2004. This increase in mean age was significant (P = 0.039) [Table 3].
The most common T stage was T3 in 2002–2004 versus T2 in 2015–2017. The most common N stage was N2 in both the time groups. The most common TNM stage was IIIB in 2002–2004 versus IIB in 2015–2017. The histological type and grade showed no change in trend between the two decades of presentation, with infiltrating ductal carcinoma-Not otherwise specified and Grade III being the most common [Table 4]. There was decrease in the proportion of hormone receptor (estrogen receptor [ER]/progesterone receptors [PR]) positivity in 2015–2017 group, which was statistically significant (P = 0.047). There was a significant increase in proportion of HER-2-neu-positive cases in 2015–2017 (P = 0.043). There was a statistically significant increase in the proportion of triple-negative (TN) cases in 2015–2017 as compared to 2002–2004 (P = 0.033). Mean age of the overall TN patients was 38.2 ± 3.1 years. 83% of TN women were premenopausal [Table 5].
| Discussion|| |
This study was conducted with an aim to evaluate the patient and disease profile of breast cancer patients presenting in 2002–2004 and 2015–2017 and to evaluate the change in trend.
The median age at diagnosis for breast cancer among Indian women is generally between 40 and 50 years. Indian women are about 6–18 years younger than their western counterparts. The early onset in Indian women could be explained by an age-period-cohort effect: i.e., the rapid change of breast cancer risk profiles allied to westernized lifestyle such as low parity, insufficient breastfeeding, and weight gain is observed more commonly in younger women that has resulted in a higher increase of breast cancer in the younger generation. Another possible cause may be the high young population density of this country.
In our study, there was earlier mean age at presentation in 2015–2017 as compared with 2002–2004. While only 39.40% of patients were <45 years in 2002–2004, the number increased to 57.33% in 2015–2017. This shows that patients are now presenting at younger age with only 18.66% of patients presenting at more than 55 years. Breast cancer at a young age is known to behave more aggressively with worse results. Tumors in young people again have higher grade, increased possibility of lymphatic metastases, and hormone receptor negativity increasing the aggressiveness of tumor biology of patients in our study in the current decade.
Results from large case–control and cohort studies conducted among women from Southeast Asian countries suggest that women who are unmarried, nulliparous or with a reduced number of full-term pregnancies, older at first full-term pregnancy, have not breastfed are at increased risk for breast cancer. Women menstruating at age <12 years have increased risk of developing breast than those menstruating above 12 years. Similarly, women achieving menopause after 55 years have increased risk since their longer period of menstruation leads them to higher lifetime exposure of hormones, estrogen and progesterone., In our study, although the mean age at menarche and menopause showed no significant change over a decade, there was a significant increase in the premenopausal presentation in 2015–2017 (65.33%) as compared to 2002–2004 (44.11%). There was a significant increase in the mean age at first childbirth in 2015–2017 against 2002–2004. There was also increase in nulliparity in 2015–2017 (23.33%) compared to 2002–2004 (14.70%). Multiparity decreased from 61.76% in 2002–2004 to 40% in 2015–2017. Breastfeeding at least for 6 months was less in 2015–2017 (74.78%) as compared to 2002–2004 (93.10%). However, these changes were not significant.
Based on time-trend analyses of national health data or ecologic studies, it has been posited that changes in dietary habits to a more western style (i.e., higher intake of calorie, fat, animal protein) correlate with an increased breast cancer incidence among Indian women. Obesity again is an established risk factor for breast cancer among Southeast Asian women, with higher BMIs having a 1.5- to 2.0-fold higher risk of breast cancer. In Manipur, the mean BMI of female cancer patients is 28.2. In our study, the mean BMI increased from 24.13 in 2002–2004 to 28.45 in 2015–2017. Overweight patients increased from 44.11% in 2002–2004 to 65.335 in 2015–2017, thus increasing the risk of breast cancer.
A study by Wani et al. in 2012 observed stage IIB as the most common stage, followed by stage IIIA and stage IIIB, while Saxena et al. observed stage IIIB as the most common followed by stage IIIA and stage IIB in 2000. Our study follows a similar pattern with stage IIIB being the most common in 2002–2004 and stage IIB being the most common in 2015–2017. In 2002–2004, 27.93% of the cases were in early stage, while in 2015–2017, 42.65% of the cases were in early stage. Of the advanced cases of our study, 77.7% of patients were below 50 years of age confirming that the disease is more aggressive in younger age group.
ER is a well-established predictive and prognostic factor in breast cancer. Therefore, testing for ER and PR status is critical to planning optimal treatment in breast cancers. According to Desai et al., the receptor positivity rates are lower in Indian population than in Western countries. This is probably due to the high prevalence of high-grade tumors among the study population. The Nottingham grade and the mitotic count have a significant inverse correlation with the Quick Score of hormone receptor expression. The presence of necrosis and lymph vascular invasion shows an inverse relationship with ER and PR reactivity. In our study, ER and PR positivity rates were 58.81% in 2002–2004 and significantly decreased to 43.32% in 2015–2017. Grade III tumors being the most common in both decades, our study is in concordance with the above data.
Again, ER and PR were inversely related to HER-2/neu overexpression, whereas tumor grade was positively associated with HER-2/neu overexpression. Some studies reported that HER-2/neu overexpression tends to decrease with age. Majority of the studies on Indian patients during the present decade showed increasing trends and reiterated the fact that majority of the Indian breast cancer patients are still ER and PR negative in spite of the changes in the interpretation guidelines in 2010., In our study, HER-2-neu-positive cases were significantly higher in 2015–2017 as compared to 2002–2004.
TN breast cancer is associated with younger age, higher histological and nuclear grade, and high levels of p53 and Ki-67 expression. These characteristics are known to be cancer biomarkers of biologic aggressiveness and poor prognosis in breast cancer. Previous studies among Northeast Indian women have reported more than 30% of breast cancer with the TN subtype., In our study, there was significant increase in proportion of TN patients over a decade. Mean age of all TN patients was 38.2 years, with 87% of them being premenopausal.
| Conclusion|| |
In the Northeast region of India, Papum Pare district in Arunachal Pradesh recorded the highest age-adjusted ratio (AAR) in breast cancer. Manipur state as a whole recorded AAR of 9.7/100,000 population. Again, the 5-year survival of cases in the northeast is inferior to the rest of India. Keeping in mind the gravity of the situation, an attempt was made to bring out the change in the trends of the clinical, pathological, and demographic profile of breast cancer over a decade. Our study has shown that there is increased incidence of breast cancer in younger women over the period of time. Significant change in mean age at presentation, locality, premenopausal status, parity, age at first childbirth, and stage at presentation was seen over the years. More aggressive biological behavior of tumors with receptor negativity and HER-2-neu positivity became the trend. Thus, we need to have a relook at the strategy to manage breast cancer in the coming future. The exact cause of the change in disease and patient profile is not known, and further studies will be required to establish the concept and see the further change in trends.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Global Burden of Disease Cancer Collaboration, Fitzmaurice C, Akinyemiju TF, Al Lami FH, Alam T, Alizadeh-Navaei R, et al
. Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 29 cancer groups, 1990 to 2016: A systematic Analysis for the global burden of disease study. JAMA Oncol 2018;4:1553-68.
India State-Level Disease Burden Initiative Cancer Collaborators. The burden of cancers and their variations across the states of India: The global burden of disease study 1990–2016. Lancet Oncol 2018;19:1289-306.
National Centre for Disease Informatics and Research, National Cancer Registry Programme, ICMR. A Report on Cancer Burden in North Eastern States of India 2012-2014. Bangalore, India: NCDIR-NCRP (ICMR); 2017.
Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al
. Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 2015;136:E359-86.
Murthy NS, Agarwal UK, Chaudhry K, Saxena S. A study on time trends in incidence of breast cancer – Indian scenario. Eur J Cancer Care (Engl) 2007;16:185-6.
Malvia S, Bagadi SA, Dubey US, Saxena S. Epidemiology of breast cancer in Indian women. Asia Pac J Clin Oncol 2017;13:289-95.
Laishram RS, Jongkey G, Laishram S, Sharma DC. Clinicomorphological patterns of breast cancer in Manipur, India. Int J Pathol 2011;9:40-3.
Rajbongshi N, Mahanta LB, Nath DC, Sarma JD. A matched case control study of risk indicators of breast cancer in Assam, India. Mymensingh Med J 2015;24:385-91.
Chopra B, Kaur V, Singh K. Age shift: Breast cancer is occurring in younger age groups: Is it true? Clin Cancer Investig J 2014;3:526-9. [Full text]
Mousavi-Jarrrahi SH, Kasaeian A, Mansori K, Ranjbaran M, Khodadost M, Mosavi-Jarrahi A. Addressing the younger age at onset in breast cancer patients in Asia: An age-period-cohort analysis of fifty years of quality data from the international agency for research on cancer. ISRN Oncol 2013;2013:429-862.
Chauhan A, Subba SH, Menezes RG, Shetty BS, Thakur V, Chabra S, et al
. Younger women are affected by breast cancer in South India – A hospital-based descriptive study. Asian Pac J Cancer Prev 2011;12:709-11.
Ali I, Wani WA, Saleem K. Cancer scenario in India with future perspectives. Cancer Ther 2011;8:56-70.
Agarwal G, Pradeep PV, Aggarwal V, Yip CH, Cheung PS. Spectrum of breast cancer in Asian women. World J Surg 2007;31:1031-40.
Wani SQ, Khan T, Wani SY, Koka AH, Arshad S, Rafiq L, et al
. Clinic-epidemiological analysis of female breast cancer patients in Kashmir. J Cancer Res Ther 2012;8:389-93.
Saxena S, Rekhi B, Bansal A, Bagga A, Chintamani, Murthy NS. Clinico-morphological patterns of breast cancer including family history in a New Delhi hospital, India – A cross-sectional study. World J Surg Oncol 2005;3:67.
Paymaster C, Gangadharan JC. Epidemiology of breast cancer in India. J Natl Cancer Instit 1972;48:1021-24.
Desai SB, Moonim MT, Gill AK, Punia RS, Naresh KN, Chinoy RF. Hormone receptor status of breast cancer in India: a study of 798 tumours. Breast 2000;9:267-70.
Kumar RV, Panwar D, Amirtham U, Premalata CS, Gopal C, Narayana SM, et al
. Estrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2 status in breast cancer: A retrospective study of 5436 women from a regional cancer center in South India. South Asian J Cancer 2018;7:7-10.
] [Full text]
Chatterjee K, Bhaumik G, Chattopadhyay B. Estrogen receptor and progesterone receptor status of breast cancer patients of eastern India: A multi-institutional study. South Asian J Cancer 2018;7:5-6.
] [Full text]
Singhai R, Patil AV, Patil VW. Cancer biomarker HER-2/neu in breast cancer in Indian women. Breast Cancer (Dove Med Press) 2011;3:21-6.
Shankar A, Roy S, Rath G, Kamal VK, Bhandari M, Kulshrestha R, et al
. Change in trend in various clinico-pathological factors and treatment profile of breast cancer patients: A tertiary cancer centre experience. Asian Pac J Cancer Prev 2016;17:3897-901.
Laishram RS, Nepram SS. What's positive about triple negative breast cancers. J Med Soc 2015;29:61-3. [Full text]
Sharma M, Sharma JD, Sarma A, Ahmed S, Kataki AC, Saxena R, et al
. Triple negative breast cancer in people of North East India: Critical insights gained at a regional cancer centre. Asian Pac J Cancer Prev 2014;15:4507-11.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]