Cancer of breast is the most common cancer affecting women worldwide, and is the second most common cause of cancer death next to lung cancer¹. Breast cancer is the most common malignancy in women and is the leading cause of cancer mortality worldwide. It is responsible for more than 500,000 deaths annually². In urban Indian population breast carcinoma is the most common cancer among women. It is second to cancer of cervix in the rural population, based on national cancer registry data (2006)³. The incidence of breast cancer is steadily rising in India. As per the ICMR-PBCR data, breast cancer is the commonest cancer among women in urban registries of Delhi, Mumbai, Ahmedabad, Calcutta, and Trivandrum constituting more than 30 percent of all cancers in females³.

 Over 100,000 new breast cancer patients are diagnosed annually in India. The incidence is higher in urban areas being 1 in 22 in a lifetime compared to rural areas, where this risk is relatively lower being 1 in 60.⁴ In India, 50-70% of breast cancer patients present at an advanced stage⁵. Breast carcinoma is a disease of diversity and it can be categorized into subtypes with distinct biological features.   The main motive behind the evaluation of such a newly detected palpable lump is basically to rule out malignancy. Evaluation of a breast lump involves the rational use of a detailed history, clinical breast examination, imaging modalities and tissue diagnosis⁶. A confident diagnosis can be made in 95% of cases through a combination of clinical examination, imaging and fine needle aspiration cytology ( FNAC)⁷.

Hormone receptor status of a given breast cancer (ER, PR) provides information about the particular genetic type of cells which have become malignant and an indication of how the breast carcinoma will likely respond to chemotherapy and endocrine therapy (hormone related therapy), if required. Her2neu is a tumour biomarker associated with disease progression and metastatic potential. Ki67 is a proliferation marker which shows how fast the tumour is growing, whether or not there is evidence of cell damage and death. The incidence of carcinoma breast patients has increased over a period of few years, reason being either increased awareness or early diagnosis.

Breast cancer is a disease of old age with peak incidence in the fifth and sixth decades in the western countries, but in India the disease is seen a decade earlier, probably because of shorter life expectancy in Indian women (about 65.3 years as per Indian data in 2005)⁸. The risk factors for breast cancer in western population include late age of childbirth, nulliparity, smaller duration of breast feeding, smoking etc. while in India early menarche and late menopause are the risk factors and longer duration of breastfeeding, early childbirth and multiparity are protective factors⁸.

Aims and objectives

The purpose of this study is to assess the profile of carcinoma breast patients based on their clinical, histopathological and tissue biomarker status comparing it with that of the other parts of the world.

This was a hospital based study. Thirty patients of breast cancer were studied after taking informed consent. Patients who had already undergone surgery for breast carcinoma outside this hospital or who were admitted only for radio or chemotherapy were not included in this study. Detailed history of the patients were taken including their age, marital status, occupation and their chief complaints of having either lump or pain whether cyclical or non cyclical or ulcer or any discharge or retraction from nipple. Duration, position and mode of onset of lump were asked. History regarding loss of weight, bony pain, shortness of breath, seizures, jaundice etc. were also asked. Detailed personal history including menstrual history, parity, age at menarche, age at marriage, age at menopause, age at first child birth, duration of breastfeeding after each child birth, history of oral contraceptives, hormone replacement therapy, smoking and alcohol were taken. A complete medical, surgical as well as family history of the patient was taken. Any history of malignancy in family was enquired about. Thorough general physical examination of the patients were done. Detailed local examination of the patients were done. First normal breast was examined followed by breast with the pathology. This was followed to have an idea of the patient’s normal architecture and consistency of the breast. Breast examination was followed by examination by examination of axilla, arm and thorax. Any enlarged lymph node or lymphedema of the arm was noted. Histopathological examinations included fine needle aspiration cytology(FNAC) of the patients or corecut biopsy. For biomarker profile patients were subjected to estrogen and progesterone receptor, HER2NEU receptor and ki67 marker.

Thirty patients were included in this study. Age of patients ranged
from 32-81years. Mean age of presentation was 48.8+11.87years.

All 30 patients had lump as their clinical presentation. 8 patients presents with pain in the breast. 2 patients had ulcer as their chief complaint. 5 patients had associated weight loss.

2 patients had nipple discharge and 5 patients had nipple retraction. Enlarged lymph nodes were present in 20 patients. Concurrent risk factor associated with carcinoma breast in our study was early menarche which was present only in 2 out of 30 patients.

Age at first child birth more than 30 years is a risk factor. 2 patients had this risk factor.
None of the patients in our study had late menopause.

None of the patients out of 30 had used oral contraceptive pills. 

None of the patients had history of prior radiation exposure.

2 patients had not breast fed their children.

In our study, it was seen that 60% of the patients had lump on the left side and 40% had lump on right side.

In our study, out of 30 females, 10 patients had early breast cancer (33.33%). 19 patients (63.33%) had locally advanced breast cancer. This was the most common type of cancer in our study. In metastatic group, 1 patient was present.

 In our study, 30 (100%) patients had invasive ductal carcinoma not otherwise specified either on FNAC or core needle biopsy.

In our study,43.33% patients were ER positive and 56.67% patients were ER negative. 23.33% of the total patients were PR positive and 76.67% patients were PR negative. HER2 positive patients were 43.33%.  HER2 negative patients were 56.67%.

In the present study, 22(73.33%) patients had less than 10% KI positivity.  2 patients (6.67%) had more than 40% KI positivity.

In our study, 30% patients were triple negative which was the most common molecular type of carcinoma breast.  8 out of 30 (26.67% )patients were in LUMINAL A group followed by LUMINAL B group , 6 out of 30(20%).

DISTRIBUTION OF AGE IN PATIENTS

TABLE NO. 1

CLINICAL PRESENTATION

TABLE NO. 2

RISK FACTORS

TABLE NO. 3

LOCATION OF THE LUMP

TABLE NO. 4

CLINICAL CLASSIFICATION

TABLE NO.5

In our study, out of 30 females, 10 patients had early breast cancer (33.33%).

19 patients (63.33%) had locally advanced breast cancer. This was the most common type of cancer in our study.

In metastatic group, 1 patient was present.

HISTOPATHOLOGICAL TYPES

TABLE NO. 6

HORMONE RECEPTOR STATUS

TABLE NO. 7

KI 67 STATUS

TABLE NO.8

IMMUNOHISTOCHEMICAL SUBTYPES

TABLE NO. 9

CLASSIFICATION OF BREAST CANCER ACCORDING TO MOLECULAR MARKERS

Based on ER, PR and HER2/neu status, breast cancers can be divided into 4 major categories.

1. Luminal A – This includes cases with ER+ve/PR+ve, ER+ve/PR-ve, ER-ve/PR+ve and HER2/neu –ve status.
2. Luminal B – This includes cases with ER+ve/PR+ve, ER+ve/PR-ve, ER-ve/PR+ve and HER2/neu +ve.
3. HER2/neu positive – This includes the cases which were ER-ve/PR-ve and HER2/neu is +ve.
4. Triple negative – This includes cases which are negative for all the receptors, ER-ve, PR-ve and HER2/neu -ve.

Table No: 10

In our study all of the patients were females 30 (100%). There was no male patient in our study. Breast cancer is a disease which is seen most commonly in
female patients, with less than 1 % being males. Al-Ahwal in Pakistan in their study observed that majority of the cases were females (98.9%), only 1.1% being male patients. Ghosh et al in their study of 2001 cases at a tertiary hospital at Mumbai observed 98.8% cases were of females and 1.2 % cases were of male patients⁹. The incidence of male patients in our present study was slightly lower than these studies. This disparity could be due to large study size in both the above studies. Regarding  age,  in a study of 260 cases in Pakistan, Al-Ahwal also observed that maximum patients were in the age group of 41-60 years¹⁴. 

In a study conducted on 321 cases of carcinoma breast, in Chennai by Ambroise et al, it was observed that the patient age ranged from 24-99 years with a mean age of 53.8 years¹⁰. 

Li et al conducted a nationwide study on 4211 cases of carcinoma breast in China. They reported the mean age at the time of presentation to be 48.7 years¹¹.

 Pathak et al in their study conducted on 136 cases in Nepal reported the mean age to be 48 years (range 21 -80 years)¹². The results of these two studies were
comparable with the results obtained in our study.

 In our study, 13 (43.3%) patients had tumour in upper outer
quadrant and 4 patients (13.3%) had tumour in upper inner quadrant.
1 (3.3%) patient had in lower outer quadrant. 1(3.3%) patient had
tumour in lower inner quadrant and 7 (23.3 %) patients had tumour in
central quadrant. Similar location of tumour in carcinoma breast has also been shown by Fischer B, Slack NH et al in their study on carcinoma breast¹³.

Regarding histological type, Bhagat et al observed Infiltrating duct carcinoma (NOS) in 94.83% of the cases followed by medullary and mucinous carcinoma in
3.44% and 1.72% cases each in his study in Gujarat¹⁵. Jain et al also reported Infiltrating duct carcinoma as the major histopathological type (91.1%)¹⁶. The results of these studies were comparable with our study.

 Eun Hwa Park et al in Korea in 2014 observed IDC to be the most common histopathological type of carcinoma breast¹⁸. Harhra et al in Yemen also found  IDC to be the most common histopathological type, consistent with our study¹⁷.

Therefore IDC, NOS is the most common subtype of breast cancer reported in various studies in literature and the result of present study is consistent with this observation. Regarding ER positivity,  Bhagat et al in their study conducted at Surat, Gujarat found out 48.27% of the cases to be positive for estrogen receptor¹⁵. In a study conducted at Jaipur by Jain et al on 203 patients, they found out 37.4% of the cases to be ER positive¹⁶. Nikhra et al, in their study done at Vadodara, Gujarat reported ER positivity in 39.5% of the cases¹⁹. The above three studies showed results of ER positivity which were comparable with our present study.

Regarding PR positivity, Pathak et al found out PR positivity in 19% of the cases. This study was done in Nepal and the results were slightly lower than our present study¹².
Ahmed et al found PR positivity in 27% of the cases²⁰.  Bhagat et al reported PR positivity in 37.93% cases¹⁵.  Nikhra et al in their study found out 41.8% cases to be PR positivity¹⁹. These studies conducted in India showed results comparable to our present study.

Regarding HER positivity, In the studies conducted by Rajesh NG and Ambroise et al, HER-2/neu positivity was seen in 27.9% and 27.1 0% cases respectively^9,10. These results were  lower than the present study, this could be due to the larger study population in the two studies.  Jain et al reported HER-2/neu positivity in 35% cases¹⁶.

Nikhra et al observed HER-2/neu positivity in 32.5% of the cases¹⁹. The results of both the studies were comparable with the present study. Sharma et al observed HER-2/neu positivity in 32.5% of the cases¹⁹. This result was comparable with the present study.

A significant number of cases in the present study comprised of TNBC cases. 30% cases belonged to this category. This observation was comparable to other studies conducted in India by Ghosh et al, Sharma et al, Nikhra et al where the incidence of TNBC was 29.8%, 31 .9% and 31 .7% respectively. Therefore, it may be inferred that TNBCs are the most common molecular group of breast cancer prevailing in India.

This  KI67 interpretation of our study is comparable with the result of Inwald et al   whose  retrospective study also showed that 57% of  the patients with KI67 positivity below  15% had better prognoses^.2

^{COMPARISON OF MEAN AGE OF PATIENTS}

IDC (NOS) COMPARISON

COMPARISON OF ER POSITIVITY

COMPARISON OF PR POSITIVITY

COMPARISON OF HER2NEU POSITIVITY

COMPARISON OF TNBC

KI SCORE INDEX COMPARISON

To conclude, this study shows that carcinoma breast is a disease with a gender bias, more commonly affecting females. This study shows that this part of subhimalayan region have their patients in their thirties or forties which is comparatively earlier in comparison to their western counterparts. The most commonly involved quadrant of the breast in this region is upper-outer quadrant, which is an established fact. Regarding clinical presentation, lump in the breast is the most common presentation. Histopathogical subtype which is the most common in this part is Invasive Ductal Carcinoma(NOS). Patients usually present as locally advanced type which is also different from western world. Triple negative breast cancers are more common in this region while in other parts of the world, Luminal A is the commoner subtype. Thus, the present study concludes that the carcinoma breast in this part of India is has different clinical and molecular presentation from that of other parts of the world.

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