|Ahead of print
Breast cancer in Andaman and Nicobar Islands: A retrospective analysis
PP Abdul Shahid1, Lena Charlette Stephen2
1 Department of General Medicine and Consultant Medical Oncologist, Andaman and Nicobar Islands Institute of Medical Sciences, Port Blair, Andaman and Nicobar Islands, India
2 Department of Community Medicine, Andaman and Nicobar Islands Institute of Medical Sciences, Port Blair, Andaman and Nicobar Islands, India
|Date of Submission||30-Oct-2018|
|Date of Decision||21-Jan-2019|
|Date of Acceptance||22-Jan-2019|
|Date of Web Publication||08-Jul-2020|
Lena Charlette Stephen,
Department of Community Medicine, Andaman and Nicobar Islands Institute of Medical Sciences, Port Blair, Andaman and Nicobar Islands
Source of Support: None, Conflict of Interest: None
Background: Breast cancer is the most common cancer in India among women. This study was conducted to describe the demographic, clinical, histopathological, endocrinological and survival pattern of breast cancer patients in Andaman and Nicobar Islands.
Methods: The study was done in Medical Oncology department of GB pant hospital. Data was retrieved from the case sheets of patients who consulted from 1st February 2015 to 31st January 2018. As this hospital is the only referral hospital, the patients are representative of all cancer patients in the Island, and the population base is well defined.
Results: During the study period, 85 breast cancer patients were treated. Of the 82 female patients, the standardized incidence rates in 2015, 2016 and 2017 were 8.82, 13 and 14.42 per 100,000 women respectively. The prevalence and mortality rates in 2015, 2016, 2017 were 14.88, 27.96, 40.37, and 1.1, 2.74, 0.55 per 100,000 women respectively. Metastasis was detected at the time of diagnosis in 18.8% of patients. Estrogen receptor (ER) and progesterone receptor (PR) positivity was reported in 55.9% of patients, HER 2 positivity in 28.1% and triple negativity in 27.3%. The overall survival at 12, 24, and 36 months follow-up were 88.9%, 84.3% and 52.7% respectively. In univariable analysis, the hazard ratios were significantly higher for patients with metastasis and diagnosis before 2015.
Conclusion: As compared to the country, breast cancer incidence was lower in the Islands with better survival. Stage at diagnosis was the most important factor determining survival in these patients.
Keywords: Breast neoplasms, epidemiology, survival
| » Introduction|| |
According to the GLOBOCAN 2018, the incidence of breast cancer among women in India was lower than the global rates, but the mortality rates were comparable. Globally, breast cancer was the most common cancer among women and the second most common cancer in both genders. However, in India, breast cancer was the most common cancer among women and in both genders. The age-standardized incidence and mortality rate of breast cancer globally were 46.3 and 13 per 100,000 women, respectively; whereas, in India, they were 24.7 and 13.4 per 100,000 women, respectively. According to National Cancer Registry Programme, breast is the leading site of cancer among women in most hospital-based cancer registries and in urban population-based cancer registries in India.,
Literature review indicates that, in India, the burden of breast cancer has been increasing with time., The demographic, clinical, histopathological, endocrinological, and survival pattern of patients with breast cancers across the country was different. Most patients diagnosed at 40-60 years[5–8] belonged to stage II or III at diagnosis[5–7] and histopathologically were infiltrating ductal carcinoma.,,, Studies also revealed that the assessment of hormonal receptor status was not always performed for patient care, and the prevalence of estrogen receptor (ER) expression and progesterone receptor (PR) expression varied between 34% and 60%.,,,,,, The proportion of triple (ER, PR, human epidermal growth factor receptor-2 (HER 2)) negative breast cancers ranged between 18% and 46% across the country.,,, The five-year survival of breast cancer patients was between 40% and 70%., According to CONCORD-3 study, the age-standardized five-year survival for breast cancer patients in India was 66.1%.
Hence, this study was conducted to describe the demographic, clinical, histopathological, endocrinological, and survival pattern of patients with breast cancers in Andaman and Nicobar Islands.
| » Materials and Methods|| |
Andaman and Nicobar Islands (ANI) is an archipelago of 572 islands located about 1200 km away from mainland India. Administratively, ANI is divided into three divisions: North and Middle Andaman (NMA), South Andaman (SA), and Nicobar. The total population of the islands according to census 2011 was 380,581 with women comprising about 46.7% of population. The Islands are also home to six tribal groups, the largest of which is the Nicobarese tribe.
GB Pant hospital located at Port Blair is the sole referral hospital in ANI. Surgical and medical management of cancers is provided free of cost in the hospital, while patients are referred to mainland India for radiotherapy. In addition, most cancer patients of ANI at some point of time during their treatment utilize the services of the study hospital. Therefore, the number of cancer patients attending GB Pant hospital is a good approximate of the total number of cases in the Islands.
The study was conducted among patients who attended the Medical Oncology outpatient department (OPD) of GB Pant hospital. Data were retrieved from the case sheets of patients who attended the OPD from February 1, 2015 to January 31, 2018 by one of the authors and validated by the other. Data were entered using MS excel in a standard format, which contains variables such as age, address, substance abuse, family history, date of first visit date of diagnosis, side, stage of disease, sites of metastasis, histopathological features such as tumor size, type, grade lymphovascular invasion, and nodal status, receptor expression, response to treatment, date of last follow-up, and outcome.
Cancer was staged into four stages as given by American Joint Committee on Cancer. The histopathological grade was assessed using Nottingham modification of the Scarff-Bloom-Richardson grading system. The measurement of ER, PR, and HER 2 expression was performed by immunohistochemistry, and if the HER 2 expression was equivocal fluorescence in situ hybridization was done.
Ethical clearance was obtained from Institute Ethics Committee of Andaman and Nicobar Islands Institute of Medical Sciences. The data were analyzed using R v3.5.1. Crude incidence, prevalence, and mortality rates were calculated using the census population projected for the year as denominator. For calculating the age-standardized rates (ASR), direct standardization with World Standard Population was done. The 95% CI for the rate was calculated using the formula: where EF is
and d is the number of events. The 95% CI for ASR was calculated using the formula
Where wi is the standard population at group i and pyari is the person-years-at-risk. The overall probability of survival was calculated using Kaplan–Meier method. As the date of diagnosis was not known in a few patients, the period of follow-up was calculated from the date of first visit to last visit. Univariable analysis was done, and the hazard ratios were compared using the logrank test. Multivariable analysis was performed using Cox regression. All variables with P < 0.2 were included in multivariable analysis, and the variable with highest P value was eliminated sequentially.
| » Results|| |
During the study period, 85 patients of breast cancer were treated. Although a majority of patients (31.8%) were of the age group 55–65 at initial visit to the study hospital, the common age at diagnosis was 45–54 years (30.6%) years. The mean (SD) age at diagnosis was 51.19 (11.66) years (Median: 50, Range: 29–80 years). Most patients (79%) were from SA, whereas 5.9% were from Nicobar and belonged to the Nicobarese group of tribes. A family history of any cancer was found in 9.4% of the patients, and specifically breast cancer was found in 4.7%. Moreover, 17% of the patients were tobacco users mainly in the form of chewing. Hypothyroidism was found in 10.6% of the patients either at the time of initial visit or during the course of treatment.
Invasive ductal carcinoma was the most commonly occurring type (84%) and mostly of grade 2 (60.4%). Most cancers were detected in the early stage (42.35%) with 4.7% in stage I and 37.6% in stage II, followed by locally advanced stage (37.6%). Metastasis was detected in 18.8% of patients. Breast cancers were slightly more common in left side (54%). One patient had bilateral breast cancer (nonsynchronous) and another had multiple foci in the same side. ER status and PR status were available in 80% of the patients and HER 2 in 75.29% of the patients. Among the patients in whom hormonal status was available, ER positivity and PR positivity were found in 55.9%, HER 2 positivity in 28.1%, and triple negativity in 27.3%.
The intention to treat at diagnosis was curative in 81.2% of patients and palliative in 18.8%. Usually, patients received multimodal treatment. Among the 18 patients with HER 2 positivity, 12 (66.67%) received Trastuzumab [Table 1]. The mean (SD) duration of follow-up for all patients was 15.52 (11.42) months (median: 12, range: 0–39 months). During follow-up, 60% of the patients attained no evidence of disease status, while 24.7% progressed to have distant metastasis and 4.7% had stable disease. The common sites of metastasis were to bone (66.67%), followed by lungs including pleura (57.1%) and liver (23.8%). During the follow-up period, 11 (12.9%) died of the disease.
Among the 82 female patients, 14 (16.5%), 19 (22%), and 21 (24.7%) were newly diagnosed in 2015, 2016, and 2017, respectively, with age-standardized incidence rates of 8.82, 13, and 14.42 per 100,000 women. The crude incidence rate shows a sharp increase from 55 to 59 years age group [Figure 1]. The incidence, prevalence, and mortality rates are presented in [Table 2].
|Table 2: Incidence, prevalence, and mortality rates of breast cancer (per 100,000 women) in ANI|
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For survival analysis, 12 patients with less than a month of follow-up and three whose outcome was not known were excluded from the analysis. Thus, 70 (82.35%) of the patients were included. The mean (SD) duration of follow-up of these patients was 18.6 (10.08) months (median: 18, range 5–39 months). The overall survival at 12 months, 24 months, and 36 months follow-up were 88.9% (95% CI: 0.81–0.97), 84.3% (95% CI: 0.75–0.94), and 52.7% (95% CI: 0.65–0.94), respectively [Figure 2]. The survival of patients stratified by treatment intent is shown in [Figure 3].
|Figure 2: Kaplan–Meier curve of overall survival of patients with breast cancer in ANI. (Event is defined as death of the participants during study period)|
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|Figure 3: Kaplan–Meier curve of overall survival of patients in ANI stratified by treatment intention. (Event is defined as death of the participants during the study period; blue—curative, red—palliative)|
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In univariable analysis, the hazard ratio was significant for stage at diagnosis and year of diagnosis. Patients with metastatic disease (HR: 9.152, 95% CI: 2.40–34.85, P < 0.001) and diagnosed before 2015 (HR: 4.737, 95% CI: 1.21–18.57, P < 0.01) had worse survival than those with early or locally advanced disease and diagnosis after 2015. In the multivariable analysis, the model containing the variables' year of diagnosis, stage, triple negativity, and side of lesion was significant with an r2 of 0.26.
| » Discussion|| |
The incidence rate of breast cancer in the ANI was lower than the country average. According to Global burden of disease study, the age-standardized incidence rate of breast cancer in India and in Union Territories other than Delhi in 2016 was 21.6 (19.5–23.7) and 17.5 (14.3–28.4) per 100,000 women, respectively, whereas in this study the rate in 2016 was 13 per 100,000 women. The plausible explanation is that the risk factors of breast cancer may be less prevalent in ANI. However, with scarce available data, future studies are warranted to explain the lower incidence of breast cancer in the Islands.
The ASR was consistently higher than the crude rates in the study. This can be explained by the age distribution of the study population. The proportion of 10–49 year olds in the study population was higher than the standard population. The three-year crude incidence rate of breast cancer per 100,000 women was highest in SA (38.79) followed by Nicobar (24.82) and NMA (17.8). The first probable reason of this disparity could be the differences in underlying age structure of the population. In addition, among these districts, SA is predominantly urban, whereas others are rural. It is interesting to note that the rates are higher among Nicobarese, a primitive tribal group than their rural counterpart. This probably can be explained by their lifestyle.[30–33]
As comparable to the studies done across the country, the mean age at diagnosis was 51.19 years,,,, Ductal carcinoma was the most common type,,,,,,, and most commonly belonged to grade 2.,, In contrast to other studies, cancer was detected in later stages,,,,, and the proportion of patients with perivascular and lymph node positivity was higher., ER, PR, and HER 2 status were not universally available in all patients., The lack of availability of receptor testing in government sector and high cost in private sector were the reasons suggested. The proportion of ER-positive,,,, HER 2-positive,, and triple-negative patients, was within the range obtained in the studies done in other parts of the country. Male breast cancer accounted for 3.53% of the cases, which was higher than those reported at Andhra, Kolkata, and Bangalore.
The overall survival of patients was 88.6% at one year declining to 83.8% at two years. This was better than the survival reported in cancer registries across the country and Chennai but worse than that reported in Mumbai. In the univariable analysis, the year of diagnosis and the stage at diagnosis were found to be significantly associated with the survival of patients. The patients diagnosed before 2015 had greater hazard because of the following reasons: first, their duration since diagnosis was longer than those diagnosed after 2015. Since the current study began at 2015, their follow-up period before the beginning of the study was truncated. Second, it may be because of better availability of treatment facilities including hormonal therapy and monoclonal antibodies and intensive case management after 2015 in the study hospital.
This is the first study in the islands to highlight the prevalence, incidence, and survival pattern of patients with breast cancer. As the number of patients is small, the outcome assessment is reliable despite being a secondary data analysis. The limitations of the study are as follows: first, a few patients might have directly availed treatment in mainland hospitals, which would have undermined the rates. However as evident in the data, most patients turn to the study hospital for follow-up in subsequent years. Hence, the number of such patients missed can be assumed to be low. Second, as it was a secondary data analysis, missing data were frequently encountered especially in variables related to histopathology and in 17.65% of patients in outcome assessment.
Despite the limitations, the study sheds light on the epidemiology of breast cancer in ANI. The incidence of breast cancer is lower in the islands than the country. There are disparities in incidence within the islands. Cancer is usually detected late, with lymph node and perivascular invasion. Although the ER, PR, HER 2, and triple-negative proportions are similar to the studies in India, these groups do not suffer excess mortality, probably because of intensive, multimodality treatment. Stage at diagnosis is the single most important factor determining survival of these patients. Although there are methodological limitations, the overall survival at one year is better than in other parts of the country. Further research is required to corroborate the findings of this study.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2]