Breast Cancer in Young Women: Analysis of Incidence, Clinicopathological Profile and Biological Behaviour in a Tertiary Care Institute from South India

Abstract

Aims and Objectives: There is an increasing incidence of breast cancer in young women and many of these patients are considered to have more aggressive disease biology. The study aimed to find out the demographic profile, clinicopathological profile, and management details in patients under the age of 40 years treated for breast cancer in a tertiary care institute.

Materials and Methods: The study retrospectively analysed all the females with biopsy proven breast cancer treated at our oncology department between January 2012 and December 2018. Patients aged below 40 years were stratified from the total breast cancer patients. The data related to demographic profile, clinical staging, pathological staging, hormonal status and treatment details were collected from medical records for the patients and analysed.

Results: A total of 1056 biopsy proven breast cancer patients were treated during the study period. Out of which, the breast cancer patients under the age of 40 years were 161 (15.24%). The mean age at presentation was 33 years. Maximum patients were between the age group of 35 to 40 years (45.4%). Most of the patients were presented with Stage III (44%). Infiltrating Ductal Carcinoma, Grade II was the most common histologic type and grade. ER (Oestrogen Receptor) positivity seen in 49% of patients and PR (Progesterone receptor) Positivity in 49.7% and 46% had HeR2 Positivity.

Conclusion: Our study concludes that the incidence of breast cancer patients under the age of 40 years is increasing. These patients tend to have higher grade tumours, Her2 Positive and triple-negative breast cancer. Young patients presenting with breast lumps should undergo all standard screening and diagnostic investigations must be carried out for early diagnosis and proper interventions.

Introduction

Breast cancer is the most common cancer affecting women globally, accounting for 25.4% of all new cancer cases. It is the leading cause of cancer death in 103 countries including India [1]. Recent years has noted a trend of increasing incidence of young breast cancer in India and it accounts for 10-20 % of all breast cancers [2-4]. Breast cancer in young females is unique in that it serves as a poor prognostic factor due to the greater incidence of advanced stage at presentation itself a poor prognosis factor because of greater incidence of advanced stage of disease at presentation [4]. The breast cancer in young Indian women appears to be associated with aggressive histology, loss of Oestrogen and Progesterone Receptor expression, with higher propensity for relapse, distant metastasis and higher mortality [5-9].Young age at diagnosis of breast cancer has emerged world-wide as an independent factor associated with higher risk of relapse and death in several large studies, even when more aggressive therapies are administered [10-14].

The diagnosis in young females is usually delayed because of low index of suspicion, firm breasts hindering clinical and radiological interpretation also causing missing of small breast lumps. Additionally, primary care doctors may also be reluctant to advice mammography in young patients because of the involved radiation. Relatively late detection and more aggressive nature of breast carcinoma is responsible for poor outcomes in these patients [15]. Expression of key biomarkers, including endocrine receptors, HER2 and proliferation markers, appears to be different in younger patients. Recent studies have attempted to control for tumour molecular subtypes, recognizing that more aggressive subtypes are more common in younger women. Two studies suggested particularly worse outcomes in young patients compared to older women with luminal-B tumours [12, 14].

Despite the data available in the specialist literature, it is not yet clear whether breast cancers arising in young women are biologically different from those found in older women. Most of the published studies on this issue have focused on relatively large cohorts of premenopausal patients.[16-18] This was a hospital based retrospective observational study conducted to study various aspects of breast cancer occurring in patients younger than 40 years of age. Our emphasis was in analysing tumour characteristics among younger patients with breast cancer.

Materials and Methods

This was a hospital based retrospective observational study conducted at our oncology department between 2012 to 2018. Retrospective record-based analysis of all the breast cancer patients treated at our institute have been collected. Breast cancer patients under the age of 40 years were stratified from the total breast cancer population. Demographic, clinical, pathological and treatment details were collected from medical records.

Histopathology study was considered as a gold standard of diagnosis. Histopathological details and Immunohistochemistry (IHC) status (Oestrogen, Progesterone and Her2 receptors) were obtained from histopathology records. Cancer staging done as per TNM classification in American Joint Committee on Cancer Staging System. Histologic grading of breast carcinoma was performed using Nottingham Histologic Score.Treatment details including Surgery, Chemotherapy, Radiation Therapy and Hormonal Details were collected and retrospectively analysed.Data was collected and tabulated into a master sheet and statistical tests were applied to test the significance of association. The results were studied using appropriate statistical methods. Descriptive analysis and inferential analysis have been done in the study. p value less Microsoft word and excel were used for generating charts and graphs SPSS version 22 was used for statistical analysis.

Results

A total 161 patients of biopsy proven breast cancer who were below 40 years of age were included in study.The Patient and Tumour Characteristics are shown in Table 1.

Table 1. Patient and Tumour Characteristics.

Variable		Number	Percentage	p Value
Site	Right Breast	95	59	0.04
	Left Breast	66	41
	Less than 30	23	14.3	0.04
	30-35	65	40.3
	35-40	73	45.4
Stage	Stage 1	9	5.5	0.07
	Stage 2	68	42.2
	Stage 3	71	44
	Stage 4	13	8
ER	Positive	79	49	0.05
	Negative	82	51
PR	Positive	80	49.7
	Negative	81	50.3
HeR2	Positive	74	46
	Negative	87	54
	Triple Positive	74	46	0.2
	Triple Negative	82	51

Mean age of 33 years (range: 25-40 years) was noted. Most Predominant age group was 35-40 years (45.4%) and 30-35 years (40.3%). Right breast was the most common site of occurrence.

The maximum number of patients presented with Clinical Stage III 71 patients (44%) followed by stage II which comprised of 68 patients. Metastasis was seen in eight cases in which the bones being the most common site of metastasis. Core needle biopsy was the main initial modality of diagnosis. Mammogram was undertaken by all the patients. Infiltrating Ductal Carcinoma most predominant histology and Grade II was the most common grade. With regards to hormonal status, ER positivity was seen in 49% of patients and PR Positivity in 49.7% and 46% had HeR2 Positivity. 51% were Triple Negative.

In Treatment, 60% of the patients underwent Neoadjuvant chemotherapy. Surgery was the standard of treatment in all the patients. 56% had undergone Modified Radical Mastectomy (MRM) and 39% Breast Conservation Surgery (BCS). Stage III was the predominant stage in the pathologically. A total of 146 patients were undergone adjuvant radiation as a part of Breast Conservation Therapy or with high-risk features in patients who underwent MRM. 60% had received External Beam Radiation Therapy (EBRT) with a radiation dose 50 Gray in 25 fractions either by 3DCRT (3D Conformal Radiotherapy) or IMRT (Intensity Modulated Radiotherapy). Adjuvant chemotherapy was taken by 40% and hormone treatment was undertaken by 47.7% patients and Treatment Details are given in Table 2.

Table 2. Post Operative Staging and Treatment Details.

Variable		Number	Percentage	p Value
Surgery	BCS	77	51	0.45
	MRM	76	49
Post Operative Staging	Stage I	5	3	0.07
	Stage II	65	42.4
	Stage III	70	45.7
	Stage IV	13	8
Chemotherapy	Neoadjuvant chemotherapy	92	60
	Adjuvant chemotherapy	61	40
Radiotherapy	3DCRT	92	63
	IMRT	54	37

Discussion

Breast cancer in females of age 40 years and younger, is a rare and it presents a serious concern in diagnosis and adequate management of the disease in developing countries [19, 20]. Our comprehensive study represents the cohort of Young Breast Cancer patients from India. Biological age can’t be measured accurately and thus we used the ESO-ESMO guidelines age cut off as <40 years for YBC (Young Breast Cancer) to determine our study participants [21].

The incidence varies from 2 to 6% in west to 10–20% in Asia [22-25]. It was interesting to note that more than half of our study patients belonged to the 36–40 years age group. Yet, the scant literature reporting on Breast Cancer in young women is ironical. The incidence in India has been reported as per Surveillance, Epidemiology, and End Results (SEER) data analysis among Asian women 16.2% (p < 0.0001) [26]. In our study, the proportion of YBC was 15.24% which is similar to the SEER data and the other related studies [7, 27-30]. It is widely believed that breast cancer in young women is characterized by a relatively unfavourable prognosis and unusual pathological features. This was an observational study which was designed to find out the unique features of breast cancer in young female.

In our study most common presenting complaint was breast lump which was present in all the patients (100%). Breast lump was the commonest presentation of breast cancers across the various studies [31-33].

According to the SEER study, the mean age of diagnosis, was 34.8 years while in our study it was 33 years [34]. Left breast was the predominant site of occurrence 50.8%, in previous studies, [35] however in our study it was the right breast most commonly affected. Histologically, the predominance of infiltrating ductal carcinoma case reported in our study is corroborated in numerous reports in the literature databases [36,37]. Women younger than 35 have a lower rate of ductal carcinoma in situ, which was the similar observation in our study [38].

In our study Grade 2 was most common histologic grade, which is similar to the studies conducted by Papalexis P. et al and Chollet-Hinton L [39,40]. Stage III was the most common disease stage in our population, which is similar to western studies that young women are more likely to be diagnosed at a more advanced stage [41]. Six percent (6%) of women have cancer that has spread outside of the breast at the time they are first diagnosed with breast cancer [42]. Similarly, our study had 5% of the breast cancer patients had distant metastasis at presentation.

Young women are more likely to develop breast cancer with more aggressive biological features compared to older women. These features include larger tumour size, advanced tumour stage, negative hormone receptors status (ER and PR), and overexpression of the human epidermal growth factor receptor 2 (HER2), [43,44] all contributing to the poorer prognosis among young female patients with breast cancer. We had 49% cases with ER PR positivity and 46 % cases with HER2 positivity. Hormone positivity of our study population is comparable with French cohort (41.5% vs 39.8%) but with a higher HER2 positivity (46% vs 38%) [45]. In line with previous literature our study also showed that patients <40 years more often have Breast Cancer with a Triple Negative and HER2 Positive subtype [46-48].

Both immunohistochemical (IHC) and molecular classifications have been employed to address whether cancer biology defines a unique disease in young women with breast cancer [49-52]. Evaluation of these four Luminal subtypes in a cohort of 2,970 young patients, which included a subset of young women with breast cancer, indicated that there were significantly more patients with triple-negative subtypes and significantly fewer luminal A subtypes in the young patient cohort when compared with the old women [12]. Other studies have also identified luminal subtypes in older patients [53], with triple-negative subtypes overrepresented in women younger than 40 years of age [54]. The finding that young patients with tumours classified as luminal B, HER-2 enriched and triple-negative subtypes were at increased risk of relapse when compared with older patients with the same subtype [55], suggests that younger patients with breast cancer may exhibit an aggressive biology.

The trend analyses show that young patients are increasingly treated with Neoadjuvant Systemic therapy followed by locoregional treatment which is according to earlier reports [56,35]. In our analyses the most pronounced increase in the use of neoadjuvant treatment was seen in young patients with TN and HER2 positive tumours. Previous studies described that young patients are more likely to undergo mastectomy [37,57]. In our study mastectomy percentages in young patients was 56%. In conclusion, the proportion of Breast cancer in young patients appears to be higher and represent a distinct subgroup. It is alarming to note that even in the current era, more than half of the patients present at an advanced stage, high grade, triple-negative and Her 2 positive subtypes which calls for cancer awareness and escalation of screening programmes. It has many clinical and biological features that must be considered during treatment. Finally, better characterization of somatic mutations in these tumours using next generation sequencing could further identify key driver mutations that can be targeted in this challenging disease.

Acknowledgements

Nil

Funding

The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

Competing interests

There was no conflict of interests