|Ahead of print publication
Influence of hormone receptors in breast cancer survival with correlation to place of residence
Jagannath Dev Sharma1, Amal Chandra Kataki2, Manoj Kalita3
1 Department of Pathology, Dr. B Borooah Cancer Institute, Guwahati, Assam, India
2 Dr. B Borooah Cancer Institute, Guwahati, Assam, India
3 Population Based Cancer Registry Guwahati, Dr. B Borooah Cancer Institute, Guwahati, Assam, India
|Date of Submission||11-Jun-2019|
|Date of Decision||08-Oct-2019|
|Date of Acceptance||26-Nov-2019|
|Date of Web Publication||09-Oct-2020|
Population Based Cancer Registry, Dr. B Borooah Cancer Institute, Gopinath Nagar, Guwahati - 781 016, Assam
Source of Support: None, Conflict of Interest: None
Introduction: Breast cancer is commonly diagnosed cancer in women. Tumor receptors estrogen receptor (ER) and progesterone receptor (PR) are well recognized prognostic factors for breast cancer.
Materials and Method: Data from the department of pathology for the 5-year period (2010 to 2014) is used for analysis for Kamrup district of Assam, India. Kaplan Meir method was used to evaluate survival rate.
Result: The overall 5-year survival is observed as 54.6%. There is a 10.6% improvement in survival was recorded among those who living in the urban areas. The risk of death was 40% higher for those who were resides in rural areas compared to urban areas (P = 0.070). There is a 6 fold variation in survival was observed according to their stage at presentation. Hormone receptors found to be play an important role in survival outcome. Patients with ER/PR+ (positive) status have 13.6% higher survival rate than those with ER/PR-. The overall survival for ER/PR positive is 72.1% compared to 58.5% of ER/PR negative.
Conclusion: From the study it is observed that population with positive hormone receptors (ER/PR +) and living in the urban areas is experiencing survival rate.
Keywords: Breast, cancer, India, rural, urban
| > Introduction|| |
Breast cancer is the most common cancer in women worldwide.,, Breast cancer is diverse in nature and comprised different biological subtypes., Several prognostic factors for breast cancer have been well recognized.,, Molecular and genetic testing is costly and not readily available in low-medium-income countries such as India. Clinicians generally tend to rely on the low cost and readily available immunohistochemistry classification of the breast in these countries. Tumor receptors estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) are well recognized and most commonly used histopathological factors as prognostic and predictive markers.
An estimated 2,088,849 new cases (11.6% of all cancers in both sexes) and 626,679 cancer deaths (6.6% of all cancer deaths in both sexes) were occurred globally in 2018, and in the Indian context, a total of 162,468 women were diagnosed with breast cancer (27.7% of all cancers in women). Breast cancer in India is an urban problem as higher incidence rates were seen in metropolitan places. Delhi (age-standardized rates 41.0/100,000 women), Chennai (37.9), Bangalore (34.4), and Thiruvananthapuram District (33.7) occupied the top four high incidence places in India.
About 2–5-fold variation in mortality rates was observed globally; countries with higher levels of human development index have low case fatality rate, probably due to early diagnosis and advancement in treatment facilities, the survival rate of breast cancer has increased steadily in these regions., Age-standardized 5-year net survival from breast cancer was 80% or higher in 34 countries worldwide. However, breast cancer survival was lower than 70% in Malaysia (68%) and India (60%) and very low in Mongolia (57%) and South Africa (53%).
A Global Burden of Disease study published in the lancet oncology reported that of the North-Eastern states (with a population of 45 million people), particularly states of Mizoram, Meghalaya, Arunachal Pradesh, and Assam have the highest burden of cancer in terms of age-standardized incidence, mortality, and low survival rates in India.,
No long-term cancer survival series has been conducted so far in the northeastern region. This study will give valuable information on cancer survival statistics of Kamrup district and an overview of Northeast Indian population to compare with national and international statistics.
| > Materials and Methods|| |
Data were collected from the Pathology Department of Dr. B. Borooah Cancer Institute, Guwahati, India, for the 5-year period (2010–2014) for Kamrup district of Assam, India. The Kaplan–Meir method was used to evaluate the survival rate, and the log-rank test was used to compare the survival among groups. P <0.05 was considered as statistically significant at 95% confidence interval (CI).
| > Results|| |
A total of 336 women were included in the study as the vital status (alive: 65.2% [219/336] vs. dead: 34.8% [117/336]) was present for these patients. Median follow-up time is 39 months. Of the 336 patients, 212 were from the urban population and 124 from the rural population. The mean age at the diagnosis is 49 years for urban and 45 years for the rural population [Table 1]. The overall 5-year survival is observed as 54.6% [Figure 1]. The 5-year observed survival rate for Kamrup urban is 64.5% as compared to 53.9% in Kamrup rural (P = 0.070) [Figure 2] and [Table 2]. The risk of death was 40% higher for those who were resides in the rural areas of (hazard ratio [HR] = 1.40, 95% CI 0.97–2.02, P = 0.070) than to those who were living in the urban areas [Table 3].
|Table 1: Mean age at diagnosis, patient vital status, stage at diagnosis, and receptor expression with the association of urban and rural population|
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|Table 2: Five-year survival according to place of residence, stage, and hormone receptor status|
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|Table 3: Risk of death in association to place of residence and hormonal receptor status|
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The 5-year survival rate for those with localized is 76.0% compared to 50.7% of regional and only 12.8% for distant metastasis [Figure 1] and [Table 2]. Stage-wise survival shows that Stage I breast cancer had a survival rate of 81.0% compared to 19.4% of Stage IV patients [Table 2].
Hormone receptor found to be playing a significant role in survival with correlates to place of residence. Based on the hormone receptor, the overall survival rate for with positive hormone receptor has a better chance of improved survival. The 5-year survival for ER (+ve) is 66.2% versus ER (−ve) is 58.5%, similarly, prevalence ratio (PR) (+ve) is 72.1% versus PR (−ve) is 54.1%. The combined ER/PR+ overall 5-year survival rate is 72.1% (urban 63.7% and rural 82.0%) and for overall ER/PR-5-year survival rate is 58.5% (urban 60.0% and rural 57.2%) [Figure 3] and [Table 2]. About 31% lower risk of death was found for those with ER (+ve) hormonal status (HR = 0.69, 95% CI 0.31–1.49, P = 0.34) compared to those with ER (−ve) hormonal status [Table 3]. It is interesting to observed that those with ER, PR-positive status and living in rural area have a better chance of extend life compared to those were living in urban areas (ER +ve: rural, 73.3% vs. urban 59.9%, P = 0.698 and PR [+ve]: rural 82.0% vs. urban 63.7%, P = 0.470). For those who were residing in urban areas with ER- and PR-negative status has a better chance of survival compared to rural areas (ER −ve: rural, 57.2% vs. urban 60.0%, P = 0.959 and PR −ve: rural 51.8% vs. urban 56.8%, P = 0.054).
| > Discussion|| |
Immunohistochemical markers are well-known prognostic factor in breast cancer.,,, In this study, we have analyzed the influence of ER, PR, and HER2 status on breast cancer survival with correlation to place of residence (rural/urban). Survival outcome based on race, ethnicity, and socioeconomic factors has received great attention in recent years, but only a limited efforts has been identified to find disparities in survival related to geographic residency, although 69% percentage of population living in the rural places of India.
According to our findings those who were living in the urban areas and with ER/PR+ status has higher survival rates compared to rural areas. There is a 10.6% improvement in 5-year survival was recorded among those who living in the urban areas (urban 64.5% vs. rural 53.9%).
Stage, tumor grade and histology, hormone RECEPTOR status, and HER2 statuses influence the cancer survival., In our study, only 21.3% women's were found to be diagnosed with localized stage compared to 61.0% of the United States for which the 5-year survival rate is observed as 76.0% compared to 99.0% of the United States of America. There is a six-fold variation in 5-year survival was observed according to their stage at presentation (localized 76.0% vs. distant 12.8%). Stage-wise survival shows that earlier stage at presentation is the better survival. From the study, it is observed that there is no significant difference in 5-year survival for patients with distant metastasis when it comes to place of residence (urban 16.2% vs. rural 14.8%).
Globally, among all breast cancer patients, 80% were ER positive and 65% were PR positive. In our study, 53.4% were ER positive and 50.4% were PR positive, whereas 49.6% (66/133) breast cancer patients with ER/PR+ followed by 45.9% were ER/PR-breast cancer patients. Studies done on the Indian population by Narendra et al., Yadav et al., Mudduwa, and Kaul et al. also show similar results for ER/PR status. Single hormone receptor-positive tumors were rare; in our study, only 3.8% (5/133) were ER+/PR− and 0.8% (1/133) were ER−/PR+ with breast cancer. Previous studies by Maeyer et al. and Ng et al. reported that only 1.5% and 4.6% of all treated breast cancer cases were ER−/PR+ and 11.6% were ER+/PR− in their studies. ER+/PR− and ER−/PR+ tumors are diverse subtypes of breast cancer and are associated with higher risk of mortality.,,,
Hormone receptors found to be play an important role in survival outcome. In our analysis, we significantly found that hormone receptors with positive (ER/PR+) status have 13.6% higher survival rate than those who were with negative hormonal status (ER/PR−). The overall survival for ER/PR positive is 72.1% compared to 58.5% of ER/PR negative (P = 0.1290). Remarkable results were observed for those who were with positive hormonal status (ER/PR+) and living in the rural areas observed as 18.3% higher 5-year survival (rural 82.0% vs. urban 63.7%) and 2.8% lower survival rate was found for negative hormone receptors (ER/PR−) as compared to those who living in the urban areas (rural 57.2% vs. urban 60.0%).
There was a 31% decrease chance of death found for those who were with ER-positive (HR = 0.69, 95% CI, 0.31–1.49, P = 0.343) status compared to patients with ER-negative status. Similarly, 19% reduced the risk of death for the urban population and 43% for the rural population with ER-positive status. An overall 55% lower chance of death was noted for patients with PR positive compared to their PR-negative counterparts (HR = 0.45, 95% CI, 0.20–1.05, P = 0.06). Patients those who were living in the urban areas have 35% lower risk of death, whereas it is observed that 70% for those living in the rural areas as compared to PR-negative hormonal status patients.
| > Conclusion|| |
Difference in cancer survival was observed according to hormone receptor status and place of residence. From the study, it is evidently prove that breast cancer cases with positive hormone status had higher survival than patients with negative hormone status. From the study, also we can conclude that the population residing in the urban areas have better extended survival probability compared to the population residing in the rural areas.
The results of the study indicate the importance of receptor status in the prognosis of breast cancer and disparities in survival and with correlation to a place of residence. Further, increasing access to health-care facilities in all populations can advance the progress in the elimination of breast cancer disparities among populations.
We sincerely acknowledge the cooperation from all the sources of registration and oncologists of Dr. B. Borooah Cancer Institute, Guwahati, Assam, India.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3]