|Year : 2014 | Volume
| Issue : 4 | Page : 594-598
Retrospective analysis of clinicopathological factors and outcome in breast cancer in young women in a tertiary care hospital in India
SP Deshmukh1, AD Mane1, BP Zade2, SP Sane3
1 Department of Surgical Oncology, Ruby Hall Clinic, Pune, Maharashtra, India
2 Department of Radiation Oncology, Ruby Hall Clinic, Pune, Maharashtra, India
3 Department of Statistics, Ruby Hall Clinic, Pune, Maharashtra, India
|Date of Web Publication||1-Feb-2016|
A D Mane
Department of Surgical Oncology, Ruby Hall Clinic, Pune, Maharashtra
Source of Support: None, Conflict of Interest: None
Background: The proportion of breast cancer is rising in India. It presents at a younger age in India as compared to the western countries. Aims: This is a retrospective study of 86 breast cancer patients less than 40 years treated in a single center from June 2006 to June 2011. The aim was to assess the factors that may influence clinical outcome. Materials and Methods: Data were collected from medical records. Variables such as age, stage, surgery, chemotherapy, tumor size, grade, nodal status, perinodal extension, lymphovascular emboli, estrogen receptor, progesterone receptor, and HER-2 neu were analyzed in relation to outcome. Results: Out of total 613 breast cancer patients, 91 (14.8%) were younger than 40 years. Five were excluded due to incomplete data; hence, 86 patients were included in this study. Median tumor size was 3 cm and lymph node positivity was 56.9%. Lymphovascular emboli were positive in 48.8% and perinodal extension was positive in 41.8%. Estrogen receptor positivity was 34.8%, progesterone receptor positivity was 45.3%, and triple negativity was 45.3%. The median follow-up period was 27 months with disease free survival being 73.2% and overall survival being 87.2%. In univariate analysis, the factors significantly associated with survival were stage at presentation, presence of lymphovascular emboli, perinodal extension and grade of the tumor. In multivariate analysis grade of tumor was the only significant factor. Conclusions: In young women with breast cancer, the factors significantly associated with survival were clinical stage at presentation, the presence of lymphovascular emboli and perinodal extension and grade of tumor.
Keywords: Breast, cancer, India, young
|How to cite this article:|
Deshmukh S P, Mane A D, Zade B P, Sane S P. Retrospective analysis of clinicopathological factors and outcome in breast cancer in young women in a tertiary care hospital in India. Indian J Cancer 2014;51:594-8
|How to cite this URL:|
Deshmukh S P, Mane A D, Zade B P, Sane S P. Retrospective analysis of clinicopathological factors and outcome in breast cancer in young women in a tertiary care hospital in India. Indian J Cancer [serial online] 2014 [cited 2020 Jan 24];51:594-8. Available from: http://www.indianjcancer.com/text.asp?2014/51/4/594/175352
| » Introduction|| |
More than one million new cases of breast cancer are diagnosed in the world every year. In India, more than 100,000 new cases of breast cancer are diagnosed every year and this number is projected to be double by 2030 according to the recent GLOBOCAN cancer fact sheet 2008. While, the incidence of breast cancer was higher in the developed countries in the past, recent data shows rise in incidence in developing countries with the incidence now comparable with that of the developed countries.
As compared to the western countries breast cancer in Indian women presents at a younger age, almost a decade earlier. Hence, a significant breast cancer burden in India occurs in younger women.
Several studies have suggested that breast cancer at a younger age has a poorer outcome possibly due to more aggressive biology and a late presentation due to lack of effective screening.,,, This is a retrospective study examining the clinical presentation, histopathological features and treatment outcomes of women less than 40 years of age presenting with breast cancer for the first time to a tertiary cancer center in India.
| » Aims and Objectives|| |
This retrospective study was carried out in order to assess the clinical and pathological factors and treatment related outcomes of women below 40 years of age who presented with newly diagnosed breast cancer from June 2006 to June 2011. The impact of these factors on survival was also estimated.
| » Materials and Methods|| |
An inclusion criteria for this study was histopathogically proven non-metastatic breast cancer in women less than 40 years of age who presented between June 2006 and June 2011. Clinical data were collected from patient records including the demographics and clinical presentation. Each patient underwent mammography or sono-mammography radiological imaging and the diagnosis of breast cancer was established by using fine-needle aspiration cytology or core biopsy. Treatment details including the surgical procedure, chemotherapy details, and radiation treatment were collected from the medical records. Histopathology reports were collected from the Pathology Department and relevant information including tumor type, size, grade, nodal status, the presence of lymphovascular emboli and perinodal extension was noted. Estrogen receptor, progesterone receptor and HER-2 Neu receptor status was obtained for every patient. Follow-up information was collected from hospital records and by directly contacting the patient. Median follow-up was 27 months. Patients with incomplete data or lost to follow-up were excluded from the study. Hospital Ethical Committee approval was obtained for the study.
Statistical analysis was performed with SPSS statistical package version 17. For univariate analysis, Chi-square test and Fisher's exact test were used and for multivariate analysis, binary logistic regression method was applied [[Table 1] and [Table 2]]. A P value of <0.05 was considered as significant for all analyses.
| » Results|| |
Out of a total of 613 patients treated for breast cancer in our center between June 2006 and June 2011, 91 (14.8%) patients were below 40 years of age. Five patients were excluded due to incomplete data; therefore, only 86 patients were analyzed. The median age was 35 years. Median follow-up was 27 months.
All patients presented with a symptomatic lump except one who had nipple ulceration. One patient had bilateral breast cancer. Eight patients had a family history of breast cancer, corresponding to incidence of 9.3%. BRCA analysis was not carried out for any patient. A total of 63 patients (73.2%) had early breast cancer corresponding to clinical stage I and II. Nearly, 23 patients (26.7%) had locally advanced breast cancer, clinical stage III.
The median tumor size was 3 cm on final histopathology and this included 18 patients who had earlier received neo-adjuvant chemotherapy and had been down staged. 5 out of 18 patients (27.7%) had pathological complete response to neo-adjuvant chemotherapy.
A total of 49 patients had positive lymph nodes (56.9%).
Seventy eight patients (90.6%) had infiltrating ductal carcinoma while the remaining had other histologies such as medullary and papillary carcinoma. One patient had pure ductal carcinoma in situ.
Five patients (5.8%) had grade I tumors, 45 patients (52.3%) had grade II tumors and 36 patients (41.8%) had grade III tumors. Lymphovascular emboli were present in 42 patients (48.8%) and perinodal extension was seen in 36 patients (41.8%). 30 patients (34.8%) were estrogen receptor positive while 39 patients (45.3%) were progesterone receptor positive. HER-2 Neu receptors were positive (Immunohistochemistry3+) in 20 patients and 39 patients were triple negative (45.3%).
Forty five (52.3%) patients underwent breast conservation surgery out of which one patient underwent bilateral breast conservation. Thirty nine (45.3%) patients underwent modified radical mastectomy primarily while two patients underwent mastectomy following breast conservation due to local recurrence at a later date. Primary reconstruction was carried out in only three patients.
Neo-adjuvant chemotherapy was given to 18 patients (20.9%). Adjuvant chemotherapy was given to 63 patients (73.2%). Five patients did not receive any chemotherapy. A total of 43 patients received anthracycline based chemotherapy while 34 patients received anthracycline and taxane combination based chemotherapy. One patient received Methotrexate based regimen. In three patients, chemotherapy details are not known.
Eighty patients (93%) received adjuvant loco-regional radiotherapy as indicated. All post-mastectomy patients in whom radiotherapy was indicated received radiation therapy to the chest wall and ipsilateral supraclavicular fossa to a dose of 5000 cGy in 25 fractions over a period of 5 weeks with 6 MV photons and appropriate energy electron combination along with the use of bolus material to ensure adequate skin dose. All breast conservation surgery patients received radiotherapy to conserved breast with or without inclusion of supraclavicular fossa (as per indication) to a dose of 4500-5000 cGy over 25 fractions followed by tumor bed boost to a dose of 1500 cGy in 6 fractions.
Tamoxifen was advised to all estrogen receptor (ER) and/or progesterone receptor (PR) positive patients.
The median follow-up period for all the patients was 27 months with the disease free survival being 73.2% and overall survival being 87.2% [Figure 1]. In the univariate analysis [Table 1], factors significantly associated with survival were stage at presentation, presence of lymphovascular emboli, the presence of perinodal extension and grade of tumor. The type of surgery whether the breast conserving surgery or modified radical mastectomy did not make any difference in survival, however, there was a trend toward breast conservation patients having better survival. There was no significant difference between survivals of patients who received neo-adjuvant chemotherapy as compared to those who received adjuvant chemotherapy. However, neo-adjuvant chemotherapy helped to down stage the locally advanced tumors in order to make them operable. Nodal positivity adversely affected survival to a certain extent, but was not statistically significant. Multivariate analysis [Table 2] showed only the grade of tumor as a significant factor.
|Figure 1: Praportional bar diagram showing sensitivity pattern of bacterial isolates|
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|Table 2: Results of outcome and risk factors with univariate and multivariate analysis|
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| » Discussion|| |
The proportion of breast cancer is increasing in urban India. It presents approximately a decade earlier than the West. Whether this is a reflection of the younger population in India or a true biological difference remains to be confirmed. At present, breast cancer in women below 40 years occurs in approximately 5-7.5% of the total number of cases diagnosed every year in Western Europe and US. In Asian studies, the incidence is two-folds higher. In our study, the proportion of young patients was 14.8% of all breast cancer patients.
As there is no effective screening strategy for this age group, the presentation is almost always with a palpable lump. This was shown by our study where all women except one presented with large symptomatic lumps, majority of the tumors being T2. McAree et al., have reported a symptomatic presentation in 98.2%, while Foxcroft et al., have reported a symptomatic presentation in 93%, of all breast cancer patients less than 40 years of age.
Stage at presentation has been an important prognostic factor in all breast cancer patients including the younger population. In this study, the stage correlated with survival significantly with the majority of patients being stage I and II.
In our study, the family history of breast cancer was positive in only 9.3% of patients. Foxcroft et al., in their series of 239 patients below 40 years of age found positive family history in 13.4%. It has been identified in several studies that approximately 15-30% of young patients have BRCA one or two mutations.,, In our study BRCA studies have not been carried out.
Current literature supports the hypothesis that breast cancer is generally more aggressive in younger women than older women due to larger tumor size, higher grade, higher lymph node positivity, hormone receptor negativity with associated lymphovascular emboli.,,, In our series of 86 patients, grade III tumors accounted for 41%. In other reported studies, the incidence of grade III tumors varies from 40.7% to 69.3% in young women less than 40 years of age.,
Lymph node positivity also varies widely in different studies from 40% to 61%., Our series showed lymph node positivity to be 56.9%. There was a trend toward node negative patients' survival (94.4%) being better than node positive patients (81.6%). However, this did not reach statistical significance (P value 0.108).
Estrogen receptor status has been predominantly reported to be negative in younger patients.,,, Our study also showed a similar finding with ER negativity being 65.2% and PR negativity being 54.7%. Few studies , have shown ER negativity to be as low as 23.2-40%.
The incidence of triple negativity in our study is 45.3%. This relatively high incidence of triple negative breast cancer may be partly explained by the fact that the risk factors for triple negativity are also commonly seen in Indian population, like-high parity, young age at the time of first birth,, younger age at diagnosis, i.e., <50 years,, and lower socio-economic status.
Lymphovascular emboli (LVE) is another factor found to be associated with poor prognosis with the reported incidence varying from 25.3% to 50.9% in various series. Our study showed a LVE positivity rate of 48.8% and it was also found to affect survival adversely (P value 0.019). Similarly presence of perinodal extension (PNE) also adversely affected survival (P value 0.007). The correlation of LVE and PNE with survival was statistically significant.
The rate of local recurrence has been reported to be higher in patients younger than 40 years,, probably due to aggressive tumor biology, inadequacy of surgical excision or a genetic predisposition to developing ipsilateral breast recurrence. Several studies have reported a local recurrence rate of 10-16% in this age group., In our study, there was a local recurrence of 3.8%. The recurrences were in patients who underwent breast conservation surgery.
Addition of taxanes to anthracycline based chemotherapy is known to increase disease free survival in some subgroups of breast cancer. Sequential docetaxel as adjuvant chemotherapy for early breast cancer (TACT) TACT, a large randomized trial suggested the benefit of taxane addition may be more in ER negative and HER-2 Neu positive subgroup. In our data of young patients with breast cancer there was an advantage of addition of taxanes to patients with anthracyclines as compared to those who received anthracyclines alone, though it was not statistically significant (P value 0.33). Most patients receiving taxanes received (docetaxel, adriamycin, cyclophosphamide). TACT analysis also shows an advantage of taxanes is more in the age group of 40-49. We postulate addition of taxanes in young breast cancer patients increases survival as most of these patients are hormone receptor negative.
Prognosis of breast cancer in younger women has been shown in several studies to be worse than older women, primarily because of late stage at presentation and the aggressive tumor characteristics.,, After controlling for stage and tumor biology, age itself has been shown to be a poor prognostic factor., In contrast with this, some of the published Indian data shows an inverse relationship between survival and increase in age. Gajalakshmi et al., showed prognosis becomes poorer with an increase in age at diagnosis. A population-based study by Yeole et al., reported that younger patients (<35 years) had better survival than older patients. A hospital based study from Tata Memorial Hospital, Mumbai, India showed that the 5-year survival rates for age group ≤50 years was 81% compared to >50 years (67%) suggesting younger patients had better survival than older patients with statistical significance (P = 0.024). At a median follow-up of 27 months, our study had disease free survival of 73.2% and overall survival of 87.2%, which is comparable to the reported survival of similar age group patients in the other countries.,,,,,,
This study has several limitations of being a retrospective study with a small sample size from a single cancer center. However, it does give an idea about the disease profile of breast cancer in the relatively lesser studied younger population in India.
| » Conclusions|| |
In young women with breast cancer, the factors significantly associated with survival were clinical stage at presentation, the presence of lymphovascular emboli and perinodal extension and grade of tumor.
| » References|| |
Nixon AJ, Neuberg D, Hayes DF, Gelman R, Connolly JL, Schnitt S, et al
. Relationship of patient age to pathologic features of the tumor and prognosis for patients with stage I or II breast cancer. J Clin Oncol 1994;12:888-94.
Aebi S, Castiglione M. The enigma of young age. Ann Oncol 2006;17:1475-7.
Dubsky PC, Gnant MF, Taucher S, Roka S, Kandioler D, Pichler-Gebhard B, et al
. Young age as an independent adverse prognostic factor in premenopausal patients with breast cancer. Clin Breast Cancer 2002;3:65-72.
Chung M, Chang HR, Bland KI, Wanebo HJ. Younger women with breast carcinoma have a poorer prognosis than older women. Cancer 1996;77:97-103.
van der Hage JA, Mieog JS, van de Velde CJ, Putter H, Bartelink H, van de Vijver MJ. Impact of established prognostic factors and molecular subtype in very young breast cancer patients: Pooled analysis of four EORTC randomized controlled trials. Breast Cancer Res 2011;13:R68.
Agarwal G, Pradeep PV, Aggarwal V, Yip CH, Cheung PS. Spectrum of breast cancer in Asian women. World J Surg 2007;31:1031-40.
McAree B, O'Donnell ME, Spence A, Lioe TF, McManus DT, Spence RA. Breast cancer in women under 40 years of age: A series of 57 cases from Northern Ireland. Breast 2010;19:97-104.
Foxcroft LM, Evans EB, Porter AJ. The diagnosis of breast cancer in women younger than 40. Breast 2004;13:297-306.
Turchetti D, Cortesi L, Federico M, Bertoni C, Mangone L, Ferrari S, et al
. BRCA1 mutations and clinicopathological features in a sample of Italian women with early-onset breast cancer. Eur J Cancer 2000;36:2083-9.
Peto J, Collins N, Barfoot R, Seal S, Warren W, Rahman N, et al
. Prevalence of BRCA1 and BRCA2 gene mutations in patients with early-onset breast cancer. J Natl Cancer Inst 1999;91:943-9.
Robson M, Gilewski T, Haas B, Levin D, Borgen P, Rajan P, et al
. BRCA-associated breast cancer in young women. J Clin Oncol 1998;16:1642-9.
Wang F, Fang Q, Ge Z, Yu N, Xu S, Fan X. Common BRCA1 and BRCA2 mutations in breast cancer families: A meta-analysis from systematic review. Mol Biol Rep 2012;39:2109-18.
Fernandopulle SM, Cher-Siangang P, Tan PH. Breast carcinoma in women 35 years and younger: A pathological study. Pathology 2006;38:219-22.
Colleoni M, Rotmensz N, Robertson C, Orlando L, Viale G, Renne G, et al
. Very young women (<35 years) with operable breast cancer: Features of disease at presentation. Ann Oncol 2002;13:273-9.
Vrieling C, Collette L, Fourquet A, Hoogenraad WJ, Horiot JC, Jager JJ, et al
. Can patient-, treatment-and pathology-related characteristics explain the high local recurrence rate following breast-conserving therapy in young patients? Eur J Cancer 2003;39:932-44.
Dolle JM, Daling JR, White E, Brinton LA, Doody DR, Porter PL, et al
. Risk factors for triple-negative breast cancer in women under the age of 45 years. Cancer Epidemiol Biomarkers Prev 2009;18:1157-66.
Yang XR, Sherman ME, Rimm DL, Lissowska J, Brinton LA, Peplonska B, et al
. Differences in risk factors for breast cancer molecular subtypes in a population-based study. Cancer Epidemiol Biomarkers Prev 2007;16:439-43.
Dent R, Trudeau M, Pritchard KI, Hanna WM, Kahn HK, Sawka CA, et al
. Triple-negative breast cancer: Clinical features and patterns of recurrence. Clin Cancer Res 2007;13:4429-34.
Bauer KR, Brown M, Cress RD, Parise CA, Caggiano V. Descriptive analysis of estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-negative invasive breast cancer, the so-called triple-negative phenotype: A population-based study from the California cancer registry. Cancer 2007;109:1721-8.
Brown M, Tsodikov A, Bauer KR, Parise CA, Caggiano V. The role of human epidermal growth factor receptor 2 in the survival of women with estrogen and progesterone receptor-negative, invasive breast cancer: The California cancer registry, 1999-2004. Cancer 2008;112:737-47.
van Nes JG, van de Velde CJ. The preferred treatment for young women with breast cancer – Mastectomy versus breast conservation. Breast 2006;15 Suppl 2:S3-10.
Zhou P, Gautam S, Recht A. Factors affecting outcome for young women with early stage invasive breast cancer treated with breast-conserving therapy. Breast Cancer Res Treat 2007;101:51-7.
Ingram DM, McEvoy SP, Byrne MJ, Fritschi L, Joseph DJ, Jamrozik K. Surgical caseload and outcomes for women with invasive breast cancer treated in Western Australia. Breast 2005;14:11-7.
Ellis P, Barrett-Lee P, Johnson L, Cameron D, Wardley A, O'Reilly S, et al
. Sequential docetaxel as adjuvant chemotherapy for early breast cancer (TACT): An open-label, phase III, randomised controlled trial. Lancet 2009;373:1681-92.
Winchester DP, Osteen RT, Menck HR. The National Cancer Data Base report on breast carcinoma characteristics and outcome in relation to age. Cancer 1996;78:1838-43.
Kollias J, Elston CW, Ellis IO, Robertson JF, Blamey RW. Early-onset breast cancer – Histopathological and prognostic considerations. Br J Cancer 1997;75:1318-23.
Walker RA, Lees E, Webb MB, Dearing SJ. Breast carcinomas occurring in young women (<35 years) are different. Br J Cancer 1996;74:1796-800.
de la Rochefordiere A, Asselain B, Campana F, Scholl SM, Fenton J, Vilcoq JR, et al
. Age as prognostic factor in premenopausal breast carcinoma. Lancet 1993;341:1039-43.
Gajalakshmi CK, Shanta V, Swaminathan R, Sankaranarayanan R, Black RJ. A population-based survival study on female breast cancer in Madras, India. Br J Cancer 1997;75:771-5.
Yeole B, Kumar AV, Kurkure A, Sunny L. Population-based Survival from Cancers of Breast, Cervix and Ovary in Women in Mumbai, India Asian Pacific J Cancer Prev 2004;5:308-315.
Bertheau P, Steinberg SM, Merino MJ. C-erbB-2, p53, and nm23 gene product expression in breast cancer in young women: Immunohistochemical analysis and clinicopathologic correlation. Hum Pathol 1998;29:323-9.
Yildirim E, Dalgiç T, Berberoğlu U. Prognostic significance of young age in breast cancer. J Surg Oncol 2000;74:267-72.
Gonzalez-Angulo AM, Broglio K, Kau SW, Eralp Y, Erlichman J, Valero V, et al
. Women age ≤35 years with primary breast carcinoma: Disease features at presentation. Cancer 2005;103:2466-72.
Ahn SH, Son BH, Kim SW, Kim SI, Jeong J, Ko SS, et al
. Poor outcome of hormone receptor-positive breast cancer at very young age is due to tamoxifen resistance: Nationwide survival data in Korea: A report from the Korean Breast Cancer Society. J Clin Oncol 2007;25:2360-8.
Karihtala P, Winqvist R, Bloigu R, Jukkola-Vuorinen A. Long-term observational follow-up study of breast cancer diagnosed in women ≤40 years old. Breast 2010;19:456-61.
Peng R, Wang S, Shi Y, Liu D, Teng X, Qin T, et al
. Patients 35 years old or younger with operable breast cancer are more at risk for relapse and survival: A retrospective matched case-control study. Breast 2011;20:568-73.
[Table 1], [Table 2]
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