Patterns of Care of Breast Cancer Patients in a Rural Cancer Center in Western India

Abstract

Breast cancer is an emerging public health problem in low- and middle-income countries. The main objective is to describe the clinical characteristics and patterns of care of breast cancer patients diagnosed and treated in a rural cancer hospital in Barshi, Western India. The results from a cross-sectional study of 99 consecutive breast cancer patients diagnosed and treated between February 2012 and November 2014 in Nargis Dutt Memorial Cancer Hospital is reported. The case records of the patients were scrutinized and reviewed to abstract data on their clinical characteristics, diagnostic, and treatment details. The mean age at diagnosis of the patients was 52.8 ± 11.6 years; 83.5% of women were married, and 60.6% were illiterate. Sixty percent of patients had tumors measuring 5 cm or less. Almost half of the patients (46.4%) had stage I or II A disease and a third (36.0%) had axillary lymph node metastasis. Estrogen, progesterone, and human epidermal growth factor receptor2 receptor status were investigated in 41 (41.4%) of patients only. The median interval between diagnosis and initiation of treatment was 11 days. Modified radical mastectomy was done in 91% of patients, and nearly a third of patients who were prescribed chemotherapy did not complete treatment. The rural-based tertiary cancer care center has made treatment more accessible to breast cancer patients and has reduced the interval between diagnosis and treatment initiation. However, there are still many challenges like non-compliance to and incomplete treatments and poor follow-up that need to be addressed.

Introduction

Breast cancer is the second most common cancer worldwide and, by far, the most frequently occurring cancer among women, with an estimated 1.67 million new cancer cases diagnosed in 2012, comprising 25% of all cancers in women [1]. Breast cancer ranks as the fifth leading cause of death from cancer overall (522,000 deaths per year) and is the most frequent cause of cancer death in women in less developed regions (324,000 deaths per year, 14.3% of all cancer deaths) [1].

The incidence of breast cancer has been increasing globally over the past several decades, especially in developing regions [2–4], with the highest increase in Asian countries [5]. Similar trends were observed in India, with higher incidence reported predominantly from the urban cancer registries [4]. More than 100,000 new cases of breast cancer occur in Indian women annually [6–8], with a relatively younger age distribution. Premenopausal women constitute 50% of all patients [6]. As per data from the Indian Council of Medical Research Population Based Cancer Registries, breast cancer is the most common cancer among women in the urban registries of Delhi, Mumbai, Ahmedabad, Calcutta, and Trivandrum, where it constitutes more than 30% of all cancers in women [8–10]. The age-standardized incidence rates vary by region and ethnicity, ranging from 6.2 to 39.5 per 100,000 person-years [8–10].

Breast cancer is eminently curable if detected early and treated appropriately. Management of breast cancer requires multidisciplinary treatment due to the heterogeneous characteristics recognized on histopathology and immunohistochemistry [11, 12]. Early diagnosis and socioeconomic features can affect both survival and quality of life [13, 14]. Women from low socioeconomic strata have higher mortality rates, due to diagnosis at late stages [15, 16], when little or no benefit can be derived from any form of treatment [15]. Breast cancer survival is also related to the clinicians’ workload, experience and the availability of multidisciplinary care and a full range of treatment options [17]; breast cancer patients treated in adequately equipped tertiary care centers have significantly better survival and cosmetic outcomes [18]. Access to high-quality treatment for breast cancer is still limited in the rural areas of India.

To our knowledge, little is known about the patterns of care of breast cancer patients in rural India, because there are very few centers providing tertiary care in such settings. In this manuscript, we describe the clinical profile and patterns of care from a series of 99 consecutive breast cancer patients seen in one service (Dr ML) at the Nargis Dutt Memorial Cancer Hospital (NDMCH), a rural cancer center situated in Barshi, Western India. This center has comprehensive cancer diagnostic and treatment facilities developed with technical support from Tata Memorial Hospital, in Mumbai, the leading cancer research and treatment center in India.

Materials and Methods

Only women with histologically confirmed invasive breast cancer that attended the service of one of the surgeons (ML) at NDMCH in Barshi were included. These were partly women that presented with breast symptoms or those that were already diagnosed elsewhere and seeking treatment at the hospital. Those with breast symptoms such as lump in the breast were investigated with clinical history, clinical examination, and diagnostic tests and staging investigations such as imaging, biochemical investigations, fine needle aspiration cytology, and histopathology. Patients with proven breast cancer were staged as per the Tumeur Ganglions lymphatiques Metastases (TNM) classification of malignant tumor guidelines [19]. Flourescence in situ hybridisation and immunohistochemistry were used to determine human epidermal growth factor receptor2 (HER2), estrogen receptor(ER), and progesterone receptor (PR) status in breast cancer.

The study was conducted between February 2012 and October 2014. Each included woman was registered and assigned a serial number. The patients were interviewed for social and demographic data. The clinical data, such as gynecological and family history were abstracted from patients’ medical records.

A descriptive analysis was presented as observed counts and percentages; categorical variables were given as frequencies and proportions, and continuous variables were summarized as means or medians together with standard deviations (SD) or interquartile ranges (IQR) (25th–75th percentiles). All statistical analysis was performed using STAT14 software.

Results

The patient data on 99 breast cancer patients are summarized in Table 1. The mean age at diagnosis of the patients was 52.8 ± 11.6 years; 83.5% were married, and 60.6% did not have any formal education. Family history of breast cancer was reported in only 4.4% of the women. The mean age at first childbirth was 17.3 ± 2.8 years and 92.4% of the women reported having breastfed their babies for at least 6 months after the last childbirth. Nearly one third (32.0%) of the breast cancer patients were premenopausal, and 2.3% of them reported ever using hormone replacement therapy.

Table 1.

Patient data of the women with breast cancer

Characteristics (N = 99) *	Number (%)
Demographic data
Age (mean ± SD)	52.8 ± 11.6
< 50	38 (38.4)
≥ 50	61 (61.6)
Marital status
Unmarried	1 (1.0)
Married	81 (83.5)
Widowed	14 (14.4)
Divorced	1 (1.0)
Education
Illiterate	57 (60.6)
Primary	30 (31.9)
Secondary	5(5.3)
College	2 (2.1)
Gravida (mean)
< 5	75 (77.3)
≥ 5	22 (22.7)
Parity (mean)
0	17 (17.5)
1–4	65 (67.0)
≥ 5	15 (15.5)
Age at first child birth (mean ± SD)	17.3 ± 2.8
Menstruation in the last 12 months
Yes	30 (32.0)
No	64 (68.0)
Breastfeeding for at least 6 months for the last child
Yes	73 (92.4)
No	6 (7.6)
Hormonal intake
Yes	2 (2.3)
No	86 (97.7)
Family history of breast cancer
Positive	4 (4.4)
Negative	87 (95.6)

^*N varies between items because of missing data

SD standard deviation

Table 2 shows the tumor characteristics of breast cancer patients. Almost all the patients (99.0%) presented with a lump in the breast; 46 (46.4%) patients had stage I or II A disease. Sixty (60.6%) patients had primary tumors 5 cm or less in maximum dimension and 55 (55.6%) had no axillary lymph node metastasis. Distant metastasis was present in 1.0% of the patients. The ER, PR, and HER2/neu status were documented only for 41 (41.4%) patients; among them, 12 were ER positive, 11 were PR positive, and 32 were HER2/neu positive. Based on the status of receptors, luminal A type of breast cancer (ER/PR-positive or-negative and HER2/neu-negative) was detected in only 3 (7.3%) patients, luminal B type (ER/PR-positive or ER/PR-negative and HER2/neu-positive) in 12 (29.3%) patients; 6 (14.7%) had triple-negative breast cancer and 20 (48.8%) had HER2-enriched type (ER- and PR-negative and HER2/neu-positive).

Table 2.

Tumor characteristics of breast cancer patients

	Range	Number (%)
Tumor stage
	0	1 (1.0)
	I	10 (10.1)
	IIA	35 (35.3)
	IIB	13 (13.1)
	IIIA	7 (7.1)
	IIIB	10 (10.1)
	IV	8 (8.1)
	Unknown	15 (15.1)
Tumor size (cm)
	T0	1 (1.0)
	T1	11 (11.1)
	T2	48 (48.5)
	T3	17 (17.2)
	T4	5 (5.0)
	Unknown	17 (17.2)
Axillary lymph node
	N0	55 (55.6)
	N1	20 (20.2)
	N2	5 (5.0)
	N3	6 (6.0)
	Unknown	13 (13.1)
Metastasis
	M0	85 (85.8)
	M1	1 (1.0)
	Unknown	13 (13.1)
Laterality
	Right	41 (41.4)
	Left	57 (57.6)
	Bilateral	1 (1.0)
Symptoms at presentation
	Lump	98 (99.0)
	Skin changes	1 (1.0)
	Ulceration	1 (1.0)
	Nipple discharge	2 (2.0)
	Axillary nodes	17 (17.2)
	Symptoms of distant metastasis	4 (4.0)
Estrogen receptor
	Positive	12 (12.1)
	Negative	29 (29.3)
	Not performed	34 (34.3)
	Unknown	24 (24.2)
Progesterone receptor
	Positive	11 (11.1)
	Negative	30 (30.3)
	Not performed	34 (34.3)
	Unknown	24 (24.2)
HER2
	Positive by immunohistochemistry	31 (31.3)
	Positive by FISH	1 (1.0)
	Negative	9 (9.1)
	Not performed	34 (34.3)
	Unknown	24 (24.2)
Luminal A		3 (7.3)
Luminal B		12 (29.3)
Triple negative		6 (14.7)
HER2 type		20 (48.8)

HER2 Human epidermal growth factor receptor 2

Information related to treatment is given in Table 3. The median interval between the diagnosis and the initiation of treatment was 11 days. A total of 95 patients were treated with curative intent. Modified radical mastectomy was the most frequently performed surgery, done on 90/91 (99.0%) patients who underwent surgery. Post-operative radiation therapy was prescribed for 32 women, of whom 5 could not complete radiation therapy and 9 did not undergo any radiation therapy. None of the patients had breast-conserving surgery, and as a result irradiation of the breast was not prescribed for any of them. Of the 87 patients for whom chemotherapy was prescribed, 24 (27.6%) could not complete the prescribed regime and 8 (9.2%) did not receive it at all. Chemotherapy was advised in the neoadjuvant setting in only 9 of the 87 patients for whom chemotherapy was prescribed. From the records, it was not possible to ascertain the number of patients who had discontinued treatment due to radiation- and/or chemotherapy-induced side effects and complications. No information was recorded in the patients’ case notes about whether ER modulators such as tamoxifen were prescribed. None of the patients received targeted therapy with trastuzumab.

Table 3.

Treatment characteristics of breast cancer patients

Treatment details (N = 99*)	Number (%)
Median interval between date of diagnosis and treatment (IQR25th–75th)	11 (4,19)
Treatment intent
Curative	95 (96.0)
Palliative	1 (1.0)
Missing data	3 (3.0)
Surgical treatment
No prescribed	2 (20.0)
Modified radical mastectomy	90 (91.0)
Toilet mastectomy	1 (1.0)
Missing data	6 (6.0)
Radiation therapy
No prescribed	48 (48.5)
Prescribed	32 (32.3)
Prescribed but not received	9 (28.1)
Incomplete treatment	5 (15.6)
Treatment completed	18 (56.2)
Missing data	19 (19.2)
Radiation therapy type
Following modified radical mastectomy	29 (90.6)
Palliative radiotherapy	1 (3.1)
Missing data	2 (6.3)
Chemotherapy
No prescribed	6 (6.1)
Prescribed	87 (87,8)
Prescribed but no received	8 (9.2)
Incomplete treatment	24 (27.6)
Treatment completed	55 (63.2)
Missing data	6 (6.1)
Chemotherapy type
Neoadjuvant	9 (10.3)
Adjuvant	77 (88.5)
Missing data	1 (1.1)

^*N varies between items because of missing data

IQR interquartile range

It was not possible to obtain any information on response to treatment or on the vital status of the patients at follow-up as most of the patients did not attend NDMCH for follow up.

Discussion

Our data provide an idea of the current state of breast cancer care in a rural tertiary cancer hospital in India, despite all its limitations associated with referral biases involved in a hospital/service based study. The patients were relatively young, and almost half of them had stage I or II A disease. The low average age of breast cancer onset is a common feature in low- and middle-income countries [20], reflecting the age distribution of these populations [20, 21].

Relatively more advanced disease at diagnosis for breast cancer patients has been described previously in Asian and Indian women [6, 9, 22, 23], especially among those from low socioeconomic strata [24–30] and the less educated [25, 27–29]. The most important cause of late detection of breast cancer in rural Indian women is lack of awareness about the early symptoms of the disease [31, 32]. Lack of physical and economic access to healthcare could be additional factors contributing to the late presentation [33, 34]. Fear of a breast cancer diagnosis, cancer treatments, and partner abandonment were reportedly associated with delayed and late presentation [33]. Psychosocial and cultural variables have been linked to the stigma associated with breast cancer, which may directly influence health-seeking behaviors in women [26, 27, 32, 35]. The presentation of patients in stage II or more advanced stages could be attributed to the fact that breast screening programs and public awareness strategies are virtually non-existent in rural India. Clinical breast examination and mammography are performed very sporadically in selected institutions situated in the urban regions of India [9, 15, 23]. Rural women do not have any access to such facilities.

The median interval between the date of diagnosis and the date of treatment initiation was shorter compared with other studies [33, 36]. The shorter waiting time could be explained by the availability of the rest-house (Dharamshala) free of charge and close to NDMCH; most of the remote patients used to be accommodated there during the diagnosis and treatment period.

Among those with known receptor status, the ER/PR positivity frequencies were low compared with the rates reported in studies conducted in developed countries [37–40], The rates found here are also consistent with the previous studies conducted in India [41–44], although this might be a biased observation given the large proportion of patients in whom the receptor status could not be assessed. This higher burden of ER/PR-negative disease has been attributed to several factors, including technical failures in detecting receptor positivity, the younger age of the patients, and the advanced stage at presentation. A high frequency of HER2/neu positivity was observed in the current study, although it could be biased due to a large proportion of cases with no information. The available information suggests lower rates of HER2/neu positivity of breast cancer patients from Western countries [23]. The HER2/neu positivity reported in the earlier Indian studies ranged from 29 to 51.6% [38, 45, 46]. The observed rates of luminal B and HER2-enriched type also seem to be high and could be explained by the high rate of HER2/neu-positive breast cancer reported in our study.

The vast majority of the patients in this series could be treated with curative intent; this finding is obviously biased by the selective hospital referral patterns. It is not uncommon that patients with locally advanced disease are not taken to hospitals for care assuming futility and economic hardships associated with such care. We believe that our series is heavily biased by referral of localized and loco-regional disease amenable to surgery. Surgery in the form of mastectomy was the main modality to treat patients with breast cancer. Breast-conserving surgery was not performed on any of the women, possibly due to the more advanced disease at diagnosis, which made the women unsuitable for conservative surgery. However, there may be other reasons for not practicing breast-conserving surgery in the rural tertiary care hospital, e.g., low acceptance among patients and the challenges in ensuring compliance and high quality radiotherapy and adjuvant treatments and regular follow-up, especially in a rural setting [47, 48].

The poor compliance with systemic treatment observed in our study population is a matter of concern. A significant proportion of breast cancer patients may need adjuvant therapy with hormone or chemotherapy and/or radiation therapy. Nearly one tenth of the patients treated at NDMCH did not receive any adjuvant therapy after surgery in spite of being advised to do so by the multidisciplinary tumor board. One fourth of the patients did not complete the prescribed course of chemotherapy. The reasons for non-compliance could be medical (side effects of treatment), economic, or social. Understanding the reasons for non-compliance was not within the scope of the present study. There is a pressing need to investigate the factors that prevented the patients from completing the prescribed treatment.

More than one third of the patients did not undergo the hormone receptor tests. This could be related to financial constraints, because the patients had to pay for the hormone receptor tests. Testing for at least ER status is critical to plan optimal treatment for breast cancer. In patients with ER-positive breast cancer, use of adjuvant tamoxifen for 5 years reduces the annual breast cancer death rate by 31% [49, 50]. A major deficiency was non-documentation of details of hormone therapy, if any, was given: no information was recorded in the patients’ case notes about whether ER modulators were prescribed. However, it is possible that tamoxifen was prescribed but the prescription was not recorded in the case notes. Tamoxifen is widely available in India and is generally affordable to patients. Testing for HER2/neu receptor status has limited value because trastuzumab is far too expensive and is clearly out of reach of poor rural patients in India. However, the patients with triple-negative disease need more aggressive chemotherapy.

Our study clearly highlights the importance of having a feasible and effective data management system at tertiary care centers. India has made huge progress in computer software technology and telecommunications in recent times. The technological advancements have made such services accessible even in rural heartland areas, and they are being successfully used in many health programs. The tertiary oncology care centers may consider using appropriate data management software to maintain the patient records, update them regularly, and if possible, track the patients that are non-compliant with treatment and follow-up.

Undertaking the present study was warranted due to the limited publications on patterns of care in low- and middle-income countries. Huge efforts were made to collect clinical data during almost 3 years, and this is the first study on breast cancer patient care was given by NDMCH. However, we have identified certain limitations, like lapses in data recording and poor patient follow up. These limit the complete overview of the care provided to breast cancer patients.

In conclusion, the rural-based tertiary cancer care center has made treatment more accessible to breast cancer patients and has reduced the interval between diagnosis and treatment initiation. However, there are still many gaps, like affordability, non-compliance, and poor follow-up that need to be addressed.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.