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  Table of Contents  
ORIGINAL ARTICLE
Year : 2014  |  Volume : 51  |  Issue : 4  |  Page : 604-608
 

Young breast cancer: A single center experience


1 Department of Medical Oncology, Dr. B. R. A. Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India
2 Department of Surgical Oncology, Dr. B. R. A. Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India
3 Department of Radiation Oncology, Dr. B. R. A. Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India

Date of Web Publication1-Feb-2016

Correspondence Address:
V Raina
Department of Medical Oncology, Dr. B. R. A. Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0019-509X.175332

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 » Abstract 

Background: Breast cancer in women aged less than 35 years is uncommon and accounts for 1-2% of all breast cancer in the West. There is a paucity of data on young breast cancer from India. The aim of this study was to analyze the clinical, pathological, prognostic factors and outcome in young breast cancer patients. Materials And Methods: This analysis was performed in 251 patients aged <35 years or less (defined as breast cancer in the young), who were registered at our institute over an 11 year period between 2001 and 2011. Results: The median age was 31 years (range 18-35). Positive family history (siblings and parents) was elicited in only 10 patients. The TNM stage distribution was: Stage I was 2.5%, stage II - 20.5%, stage III - 55% and stage IV - 22%. The median clinical tumor size was 5.1 cm. Modified radical mastectomy was the most common surgical procedure and this was done in 79% of cases. 40% of tumors were high grade and 60% had pathological node positive disease. Estrogen and Progesterone and human epidermal growth factor receptor 2/neu positivity were 33% and 29% respectively. Triple negative breast cancer constituted 31% of patients. With a median follow-up of 30 months, 3 years relapse free survival and overall survival was 51% and 66%. Conclusion: Young women constituted 8% of breast cancer cases. Advanced disease at presentation and triple negativity (nearly one third of patients) results poor outcome.


Keywords: Outcome, triple negative breast cancer, young breast cancer


How to cite this article:
Gogia A, Raina V, Deo S, Shukla N K, Mohanti B K. Young breast cancer: A single center experience. Indian J Cancer 2014;51:604-8

How to cite this URL:
Gogia A, Raina V, Deo S, Shukla N K, Mohanti B K. Young breast cancer: A single center experience. Indian J Cancer [serial online] 2014 [cited 2019 Dec 9];51:604-8. Available from: http://www.indianjcancer.com/text.asp?2014/51/4/604/175332



 » Introduction Top


In India, breast cancer is the most common cancer as reported from urban cancer registries and accounts for around 30% of all cancers in females.[1] The annual age adjusted rate varies in urban population based cancer registries from 25 to 33/100,000 population and is 7.2/100,000 in Barshi, a rural based cancer registry.[1] There is thus a significant region wise variation in breast cancer in India. The median age at presentation is 51 years, this is much lower than in the West.[2] The expert's consensus of St. Gallen Conference in 1998 and 2011 concluded that age ≤35, tumor size >2 cm and histopathological grade II/III were poor prognostic factors.[3] A report from Korean Breast Cancer Society revealed that risk of death rose by 5% for every 1 year reduction in age for patients aged <35 years, whereas there was no significant correlation between risk of death and age for patients aged 35-50 years.[4] For this analysis, age less than 35 years was taken as the cut-off to define breast cancer in the young as is the consensus in many parts of the world. Breast cancer in young women is uncommon and accounts for 2% of breast cancers in West.[5] Young patients with breast cancer have more aggressive clinical and biological characteristics and less favorable outcome and is more linked to genetic predisposition when compared with the disease in older patients.[6],[7] Young women with breast cancer post-treatment have more issues such us early amenorrhea, infertility, social-psychological problems and have much higher genetic predisposition than older individuals.[8] Until date, there has been no published study from India in young women with breast. The aim of this present study was to analyze the clinical and pathological characteristics and treatment outcome of breast cancer in patients below 35 years.


 » Materials and Methods Top


The study population consisted of 251 patients with invasive breast carcinoma aged <35 years, who were registered over a period of 11 years in the Department of Medical Oncology between January 2001 and December 2011. This is a university hospital and a major referral cancer center in North India. Patient details were obtained from our computer database as well as from patient files from medical records using ICD code 50. The last follow-up was performed on 30th December 2012. Tumor staging was carried out according to the Tumor, Node, Metastasis (TNM) classification 2003. Histological grading was performed using the Scarff-Bloom-Richardson histological system. Relapse free survival (RFS) (non-metastatic patients) was defined as the time period from diagnosis to the occurrence of relapse (loco-regional/systemic) or metachronous breast cancer. Progression free survival (PFS) (metastatic patients) was defined as the time period from diagnosis to the occurrence of progression. OS was calculated from the date of diagnosis to the date of death and patients were censored on last follow-up.

Baseline categorical variables were analyzed using Chi-Square test or Fisher's exact test. Non-categorical variables were analyzed using t-test or Mann-Whitney test. RFS, PFS and OS were determined by Kaplan Meier survival curves. Log rank test was used to compare survival. Univariate and multivariate analyses were performed to identify prognostic factors for survival. Cox proportional hazards model used to calculate hazard ratios. Estimates were considered statistically significant for values of P < 0.05. SPSS version 10 (233 South Wacker Drive, 11th Floor, Chicago, IL 60606-6307) software was used for statistical analysis.

Patients with early stage disease were treated with surgery, followed by systemic treatment (adjuvant chemotherapy and endocrine therapy) and radiotherapy. Modified radical mastectomy (MRM) and breast conservative surgery (BCS) were the main surgical techniques used. Latissimus dorsi or transverses abdominis myocutaneous flap repair was performed for patients in whom a primary closure following mastectomy could not be achieved. Patients with locally advanced disease were treated with three courses of neo-adjuvant chemotherapy comprising of Docetaxel, Epirubicin and Cyclophosphamide followed by surgical assessment and remaining three cycle to be given upfront or sand witch with surgery followed by radiotherapy. Those patients who had metastatic disease at diagnosis received chemotherapy/hormonal treatment and palliative radiotherapy if and when indicated.

Adjuvant chemotherapy was given in patients in whom tumor size was greater than or equal to 1 cm or there were positive nodes irrespective of estrogen and progesterone status. Neo-adjuvant chemotherapy was giving in patients with inflammatory or locally advanced breast cancer defined as T4 or large T3 disease. FEC and docetaxel containing regimens were mainly used for adjuvant and/or neo-adjuvant chemotherapy. FEC followed by docetaxel was most commonly used protocols, consisted of 5-fluorouracil 500 mg/m 2, epirubicin 75 mg/m 2 IV, cyclophosphamide 500 mg/m 2 given every 3 weeks. Docetaxel was used at a dose of 85 mg/m 2 (monotherapy) and at a dose of 75 mg/m 2 in combination with anthracyclines. Six cycles of (docetaxel 75 mg/m 2, epirubicin 75 mg/m 2 IV, cyclophosphamide 500 mg/m 2 [DEC]) was used in metastatic or neo-adjuvant setting and four cycle of FEC followed by four cycles of docetaxel was the protocol for adjuvant treatment. Standard guidelines for assessment of chemo toxicity grade were followed for any dose reduction or delay in administering chemotherapy. Cycles were generally repeated every 3 weeks.

Patients with hormone receptor positive tumor specimens received tamoxifen at a dose of 20 mg daily for 5 years after adjuvant, neo-adjuvant or palliative chemotherapy. Adjuvant radiotherapy was given in case the tumor size greater than 5 cm or there was the lympho-vascular invasion or more than four axillary lymph nodes were involved or if breast conservation surgery had been carried out.


 » Results Top


A total of 251 patients aged 35 years or younger were diagnosed with breast cancer between January 2001 and December 2011. The median follow-up time was 30 months (range 12-60 months). The median age at diagnosis was 31 years (range 18-35 years). Only 10 patients (5.5%) had a family history of breast cancer. 232 (92.8%) patients had infiltrating ductal carcinoma. 98 patients (60%) were grade II Scarff-Bloom-Richardson, 73 patients (33%) were ER receptors positive and 53 patients were human epidermal growth factor receptor 2 (Her2/Neu) positive. 53 patients (22.08%) had metastatic disease (stage IV) at first diagnosis, 6 patients (2.5%) had stage I, 48 patients (20%) had stage II and the remaining 130 patients (55%) had stage III disease. [Table 1],[Table 2],[Table 3] summarize patient, disease and treatment characteristics.
Table 1: Patient characteristics

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Table 2: Tumor characteristics

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Table 3: Treatment characteristics

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Out of 198 patients who had localized disease, 70% had stage III disease. MRM was done in 156 (79%) patients and the rest of them were subjected to BCS. All inflammatory breast cancer patients and nearly 50% of those who had locally advanced disease were offered neo-adjuvant chemotherapy. Eighteen patients (27%) had pathological complete response to neo-adjuvant chemotherapy. Out of 133 patients who received adjuvant chemotherapy, 10 patients received 6 courses of FEC, 123 patients received sequential FEC 4 cycles followed by docetaxel 4 cycles and 3 patients received cyclophosphamide, methotrexate and 5- Fluorouracil (CMF) chemotherapy. A total of 130 patients with localized disease received adjuvant radiotherapy as per our standard protocol and 11 patients received palliative RT for metastatic disease. 33% of patient received tamoxifen in the adjuvant setting as they were ER positive. At last follow up, 80 patients (42.4%) had relapsed, lung was the most common site followed by bone and liver. The median time to relapse was 30 months. For all patients with localized disease, OS and RFS at 3 years were 66% and 51% respectively. Site of relapse and metastasis is summarized in [Table 4] and [Table 5]. At the end of the study period, 62 patients (22.49%) died. OS rate at 3 years was 89%, 70.3%, 50% and 30.8% in stage I, stage II, stage III and stage IV respectively.
Table 4: Site of first relapse

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Table 5: Upfront metastatic sites

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Tumor size, T stage, nodal stage, clinical stage, pNstage, pathological stage and triple negative breast cancer (TNBC) emerged as significant prognostic factors for RFS in univariate analysis. Only clinical tumor stage and triple negativity emerged as significant prognostic factors by multivariate analysis for RFS in non-metastatic cases. [Figure 1] showed median relapse free, OS and impact of triple negativity on survival.
Figure 1: (a) Overall survival of all patients. (b) Relapse free survival all patients. (c) Overall survival in young-triple negative breast cancer and young non-(P = 0.009). (d) Relapse-free survival in young-TNBC and young non-TNBC (P = 0.001)

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Tumor size, T stage, nodal stage, clinical stage, pathological T stage, pathological nodal stage, pathological stage and TNBC emerged as significant prognostic factors for OS in univariate analysis. However, only TNBC and clinical nodal stage were the factors found to be significantly prognostic by multivariate analysis. [Table 6] showed multivariate analysis for OS and RFS.
Table 6: Multivariate analysis for overall and relapse free survival

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 » Discussion Top


Breast cancer in young women is uncommon and represents only in 2-3% of new cases in the west.[8],[9] In Asian series, this number varies between 10% in developed and up and 24% in the developing countries.[10] In our study, 8% of breast cancer patients were aged 35 years or younger, this is significantly higher than in developed countries and reflects younger age of our population. It also could be because older patients are not being diagnosed due to poor access to health-care. Family history of breast cancer is a risk factor for breast cancer in young women. In a Swedish population-based with young breast cancer, 48% of patients had a family history of breast or ovarian cancer.[11] Positive family history is elicited in 6% of cases in the present series. Loman et al. and Aebi et al. reported that positive ER status in young patients seems to have significant higher risk of disease recurrence when compared with older premenopausal patients.[11],[12] However, Gonzalez-Angulo et al. and Abahssain et al. found that hormone receptor negativity was associated with shorter RFS and OS.[13],[14] This result was consistent with our finding. Breast cancer in young women is frequently diagnosed at an advanced stage and late presentation, this is also consisted with our study.[13] Consequently, the majority of patients in our study received MRM. A positive family history or the presence of a BRCA1/2 gene mutation will also influence decisions for mastectomy rather than breast conservation, but in our analysis BRCA testing was not done. It is reported in most studies that local recurrence is higher in younger patients receiving BCS, but it is not clear and need further validation.[15],[16] In our study, 21% of our patients with local disease received breast conservation surgery and there was no difference in local recurrence in patients who have received BCS versus MRM. The RFS, PFS and OS, are relatively low in our study than published literature might be due to late presentation, more aggressive biology, advanced stage at presentation and higher triple negativity.[17],[18] Major studies of young breast cancer aged less than 35 years have been summarized in [Table 7].[13], 14, [19],[20],[21] The majority of our patients had a low family income and educational level a, which lead to lack of medical insurance and lack of health awareness.
Table 7: Major studies of young breast cancer aged less than 35 years

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 » Conclusion Top


In India, the proportion of breast cancer in young women aged ≤35 is 8%, this proportion is much higher than the published Western figures. Advanced disease at presentation and triple negativity results poor outcome.

 
 » References Top

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Loman N, Johannsson O, Kristoffersson U, Olsson H, Borg A. Family history of breast and ovarian cancers and BRCA1 and BRCA2 mutations in a population-based series of early-onset breast cancer. J Natl Cancer Inst 2001;93:1215-23.  Back to cited text no. 11
    
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Aebi S, Gelber S, Castiglione-Gertsch M, Gelber RD, Collins J, Thürlimann B, et al. Is chemotherapy alone adequate for young women with oestrogen-receptor-positive breast cancer? Lancet 2000;355:1869-74.  Back to cited text no. 12
    
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Gonzalez-Angulo AM, Broglio K, Kau SW, Eralp Y, Erlichman J, Valero V, et al. Women age < or =35 years with primary breast carcinoma: Disease features at presentation. Cancer 2005;103:2466-72.  Back to cited text no. 13
    
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Abahssain H, Lalya I, El M'rabet FZ, Ismaili N, Razine R, Tazi MA, et al. Breast cancer in Moroccan young women: A retrospective study. BMC Res Notes 2010;3:286.  Back to cited text no. 14
    
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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.  Back to cited text no. 16
    
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Yildirim E, Dalgiç T, Berbero lu U. Prognostic significance of young age in breast cancer. J Surg Oncol 2000;74:267-72.  Back to cited text no. 17
    
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Carlson RW, Anderson BO, Chopra R, Eniu AE, Jakesz R, Love RR, et al. Treatment of breast cancer in countries with limited resources. Breast J 2003;9 Suppl 2:S67-74.  Back to cited text no. 18
    
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Livi L, Meattini I, Saieva C, Borghesi S, Scotti V, Petrucci A, et al. The impact of young age on breast cancer outcome. Eur J Surg Oncol 2010;36:639-45.  Back to cited text no. 20
    
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    Figures

  [Figure 1]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]

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