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  Table of Contents  
ORIGINAL ARTICLE
Year : 2014  |  Volume : 51  |  Issue : 2  |  Page : 167-169
 

Pregnancy associated breast cancer: An institutional 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 Publication7-Aug-2014

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.138285

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 » Abstract 

Background: Pregnancy-associated breast cancer (PABC) has been defined as breast cancer diagnosed during pregnancy or within 1 year of delivery. There is a paucity of data on PABC from India. The aim of our study was to assess the clinical-pathological parameters and outcome of PABC at Institute Rotary Cancer Hospital, All India Institute of Medical Sciences. Materials and Methods: We screened approximately 3,750 cases registered from January 2001 to December 2012 and found 26 cases of PABC. Patients' records were obtained from the computer database using International Classification of Diseases code (C-50). Results: The median age was 26 years (range 20-35). The median duration of symptoms was 11.5 months. The American Joint Committee on Cancer stage distribution was Stage I - 1, Stage II - 3, Stage III - 14 and in Stage IV - 8 patients. Median clinical tumor size is 5.5 cm. Four patients were presented with the inflammatory breast cancer. Positive family history was elicited in three patients. Twenty-one patients were diagnosed after delivery, two patients in the first trimester, two patients in the second trimester and three patients in the third trimester. Estrogen receptor (ER), progesterone receptor (PR) negativity and human epidermal growth factor receptor 2 (HER2/neu) positivity was 56% and 38%, respectively. Nearly, 40% of patients had a high-grade tumor and 70% had pathological node positivity. With a median follow-up of 33 months, 3 years relapse free survival and overall survival was 40% and 50% respectively. Bone was the most common site for systemic relapse. Conclusions: PABC constituted 0.7% of all breast cancer patients. It is associated with advanced stage at presentation. Half of them were ER/PR negative and one-third was HER2/neu positive.


Keywords: Breast cancer, outcome, pregnancy


How to cite this article:
Gogia A, Deo S, Shukla N K, Mohanti B K, Raina V. Pregnancy associated breast cancer: An institutional experience. Indian J Cancer 2014;51:167-9

How to cite this URL:
Gogia A, Deo S, Shukla N K, Mohanti B K, Raina V. Pregnancy associated breast cancer: An institutional experience. Indian J Cancer [serial online] 2014 [cited 2019 Aug 24];51:167-9. Available from: http://www.indianjcancer.com/text.asp?2014/51/2/167/138285



 » Introduction Top


Breast cancer is one of most common cancer during the pregnancy along with melanoma and cervical cancer. [1] Pregnancy-associated breast cancer (PABC) has been defined as breast cancer diagnosed during pregnancy or within 1 year of delivery. [2] Most of women of PABC present with larger tumors and have a higher incidence of lymph node metastasis at diagnosis. [3] The reason might be due to a delay in diagnosis, secondary to the engorgement and physiologic hypertrophy of the pregnant or lactating breast.

Significant controversy exists in the literature, regarding the impact of pregnancy on prognosis. Previous studies have shown that after adjusting for age and stage, survival rates are similar in both pregnant and non-pregnant women. [4],[5] On the other hand, some studies pointed out the opposite results. [6] Recently, published meta-analysis has shown that PABC is independently associated with poor over-all survival and disease free survival. [7]

Until date, there has been no published study from India on PABC. The aim of the present study was to analyze the clinical and pathological characteristics and outcome of PABC.


 » Materials and Methods Top


We screened approximately 3,750 cases registered from January 2001 to December 2012 and found 26 cases of PABC. Patient's records were obtained from the computer database using International Classification of Diseases code (C-50). Tumor staging was carried out according to the American Joint Committee on Cancer 7 th edition. Histological grading was performed using the Scarff-Bloom-Richardson (SBR) histological system. Immunohistochemical testing to determine estrogen (ER) and progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2/neu) receptor status was performed using standard procedures and stained with the monoclonal antibodies (1:400; Thermo, USA) for ER, PR and (1:100; Thermo, USA) for HER2/neu respectively. Nuclear staining> 1% of tumor cell was considered as positive for ER and PR. Patients were considered HER2-positive if immunohistochemistry (IHC) was 3+ or Fluorescence in situ hybridization (FISH) was amplified (more than 6 copies of HER2/neu gene or HER2/neu: CEP17 ratio of more than 2) by Dako Hercep Test. FISH test was performed when IHC was 2+ and it was considered positive, when amplified. Triple negative breast cancer was defined as negativity for ER, PR and HER2/neu (IHC score 0 or 1+ or FISH non-amplified).

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. Overall survival (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. Estimates were considered statistically significant for values of P < 0.05. Statistical Package for the Social Sciences (SPSS Inc., 233 South Wacker Drive, 11 th Floor, Chicago, IL) version 10 software was used for statistical analysis.


 » Results Top


The median age at diagnosis was 26 years (range: 20-35 years) and median duration of symptoms was 11.5 months. Three patients had a family history of breast cancer. Median clinical tumor size was 5.5 cm. All patients had infiltrating ductal carcinoma. Four patients were SBR Grade III. Eight patients had metastatic disease (Stage IV) at presentation, bone was the most common site followed by lung and liver. One patient had Stage I, three patients had Stage II and the remaining 14 patients had Stage III disease. [Table 1] and [Table 2] summarizes patients, disease and treatment characteristics. Two patients diagnosed in the first trimester, two patients in the second trimester, three patients in the third trimester and 19 patients diagnosed with in 1 year of delivery. ER and PR immune reactivity was positive in 11 patients. Complete hormonal profile was available in 21 cases. Staining for the HER-2/neu oncoprotein was positive in 8 of the 21 patients. Triple negativity was found in only two patients. Modified radical mastectomy was done in 11 patients. Six patients received neo-adjuvant chemotherapy with standard dose of docetaxel, epirubicin and cyclophosphamide (DEC) and 3 out of 6 patients had complete pathological response. Eleven patients received adjuvant chemotherapy and three patients received palliative chemotherapy . Twelve patients with localized disease received adjuvant radiotherapy as per our standard protocol and four patients received palliative RT for metastatic disease. Twelve patients received tamoxifen in adjuvant and palliative setting as they were ER/PR positive. At last follow-up, eight patients had relapsed. Two patients had loco regional, six patients had systemic relapse. The median time to relapse was 30 months and 3 year RFS was 40%. Eight patients presented with metastatic disease, the most common site of upfront metastasis was bone followed by lung and liver. These patients received combination regimen DEC. Median progression free period was 18 months. At the end of the study period, 10 patients were died. For all patients, survival at 3 years was 50%. Two patients were aborted (one spontaneous) in the first trimester, anthracyclines were used in second and third trimester and taxanes were used after delivery. None of them received trastuzumab. Median follow-up period was 33 months.
Table 1: Patients and disease characteristics

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Table 2: Treatment characteristics

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 » Discussion Top


Breast cancer occurring during pregnancy or with in 1 st year after delivery is considered to be PABC. It is one the most common tumor of reproductive age group. PABC is relatively rare and its incidence is 0.2-3.8%. [8] One of the previous studies has suggested that approximately 10% of breast cancers diagnosed in patients aged≤ 40 years were diagnosed during the pregnancy. [9] In recent data published by Beadle et al. in young breast cancer patients, out of 668 patients, 104 were PABC which constitute 15% of cases. [10] In our study, PABC constitutes 0.7% of total cases and 8% of young breast cancer patients (<35 years). In previous studies PABC has been associated with a genetic predisposition and a strong family history. [11],[12] In our study, we found only three patients have a positive family history. In contrast to earlier studies, our study found high ER/PR expression and HER2/neu (56% and 38%). [13],[14],[15] The prognostic and predictive role of HER2/neu in PABC is not well-defined. In our analysis none of the patients received trastuzumab upfront.

There are conflicting data on outcomes after PABC. Significant controversy exists in the literature, regarding the association of pregnancy on breast cancer. Some authors showed similar survival outcome with non-pregnant patients with breast cancer, whereas others have come out with poor outcome with non-pregnant patients. [4],[5],[6] Zemlickis et al. reviewed the 118 diagnosed with breast cancer during pregnancy with 269 non-pregnant controls. They found that the pregnant women had more advanced disease, but no difference in outcome (10-year OS of 40% for patients with PABC and 48% for those with non-PABC). [16] Ali et al. reviewed 40 cases of PABC with stage and age matched control and conclude PABC patients had a higher risk of both death and recurrence. [17] There is a lack of randomized prospective data in PABC. Recently a meta-analysis, including 30 studies, has shown that PABC is independently associated with poor overall and disease free survival with hazards of 1.84 and 1.6, respectively. [7] In our study, 3 years RFS-40% and OS-50% with median follow-up of 33 months. The possible explanation for poor outcome in PABC might be due to pregnancy is a relative state of immune suppression and associated with high estrogen/progesterone state, which could alter tumor biology and potentially make it more aggressive. Some authors have also hypothesized the role of insulin like growth factors since growth hormone play a significant role in tumor biology of PABC. [18]

It has been observed that those patients in whom diagnosis was delayed or treatment deferred until after delivery had an inferior survival compared with those who received immediate diagnosis followed treatment. There is a need for mass educational program for primary care physicians that breast symptoms during and immediately after pregnancy should be fully thoroughly examined and investigated in order to make early diagnosis and prompt treatment.


 » Conclusion Top


PABC constituted 0.7% of all breast cancer patients at our hospital and most of them presented with advanced disease. PABC remains a rare and challenging entity and more prospective randomized studies are needed to optimize treatment guidelines.

 
 » References Top

1.Antonelli NM, Dotters DJ, Katz VL, Kuller JA. Cancer in pregnancy: A review of the literature. Part I. Obstet Gynecol Surv 1996;51:125-34.  Back to cited text no. 1
    
2.Viswanathan S, Ramaswamy B. Pregnancy-associated breast cancer. Clin Obstet Gynecol 2011;54:546-55.  Back to cited text no. 2
    
3.Ishida T, Yokoe T, Kasumi F, Sakamoto G, Makita M, Tominaga T, et al. Clinicopathologic characteristics and prognosis of breast cancer patients associated with pregnancy and lactation: Analysis of case-control study in Japan. Jpn J Cancer Res 1992;83:1143-9.  Back to cited text no. 3
    
4.Ezzat A, Raja MA, Berry J, Zwaan FE, Jamshed A, Rhydderch D, et al. Impact of pregnancy on non-metastatic breast cancer: A case control study. Clin Oncol (R Coll Radiol) 1996;8:367-70.  Back to cited text no. 4
    
5.Bonnier P, Romain S, Dilhuydy JM, Bonichon F, Julien JP, Charpin C, et al. Influence of pregnancy on the outcome of breast cancer: A case-control study. Societe Francaise de Senologie et de Pathologie Mammaire study group. Int J Cancer 1997;72:720-7.  Back to cited text no. 5
    
6.Amant F, von Minckwitz G, Han SN, Bontenbal M, Ring AE, Giermek J, et al. Prognosis of women with primary breast cancer diagnosed during pregnancy: Results from an international collaborative study. J Clin Oncol 2013;31:2532-9.  Back to cited text no. 6
    
7.Azim HA Jr, Santoro L, Russell-Edu W, Pentheroudakis G, Pavlidis N, Peccatori FA. Prognosis of pregnancy-associated breast cancer: A meta-analysis of 30 studies. Cancer Treat Rev 2012;38:834-42.  Back to cited text no. 7
    
8.Wallack MK, Wolf JA Jr, Bedwinek J, Denes AE, Glasgow G, Kumar B, et al. Gestational carcinoma of the female breast. Curr Probl Cancer 1983;7:1-58.  Back to cited text no. 8
    
9.Nugent P, O′Connell TX. Breast cancer and pregnancy. Arch Surg 1985;120:1221-4.  Back to cited text no. 9
[PUBMED]    
10.Beadle BM, Woodward WA, Middleton LP, Tereffe W, Strom EA, Litton JK, et al. The impact of pregnancy on breast cancer outcomes in women < or=35 years. Cancer 2009;115:1174-84.  Back to cited text no. 10
    
11.Shen T, Vortmeyer AO, Zhuang Z, Tavassoli FA. High frequency of allelic loss of BRCA2 gene in pregnancy-associated breast carcinoma. J Natl Cancer Inst 1999;91:1686-7.  Back to cited text no. 11
[PUBMED]    
12.Johannsson O, Loman N, Borg A, Olsson H. Pregnancy-associated breast cancer in BRCA1 and BRCA2 germline mutation carriers. Lancet 1998;352:1359-60.  Back to cited text no. 12
[PUBMED]    
13.Elledge RM, Ciocca DR, Langone G, McGuire WL. Estrogen receptor, progesterone receptor, and HER-2/neu protein in breast cancers from pregnant patients. Cancer 1993;71:2499-506.  Back to cited text no. 13
    
14.Middleton LP, Amin M, Gwyn K, Theriault R, Sahin A. Breast carcinoma in pregnant women: Assessment of clinicopathologic and immunohistochemical features. Cancer 2003;98:1055-60.  Back to cited text no. 14
    
15.Azim HA Jr, Kroman N, Paesmans M, Gelber S, Rotmensz N, Ameye L, et al. Prognostic impact of pregnancy after breast cancer according to estrogen receptor status: A multicenter retrospective study. J Clin Oncol 2013;31:73-9.  Back to cited text no. 15
    
16.Zemlickis D, Lishner M, Degendorfer P, Panzarella T, Burke B, Sutcliffe SB, et al. Maternal and fetal outcome after breast cancer in pregnancy. Am J Obstet Gynecol 1992;166:781-7.  Back to cited text no. 16
    
17.Ali SA, Gupta S, Sehgal R, Vogel V. Survival outcomes in pregnancy associated breast cancer: A retrospective case control study. Breast J 2012;18:139-44.  Back to cited text no. 17
    
18.Thordarson G, Slusher N, Leong H, Ochoa D, Rajkumar L, Guzman R, et al. Insulin-like growth factor (IGF)-I obliterates the pregnancy-associated protection against mammary carcinogenesis in rats: Evidence that IGF-I enhances cancer progression through estrogen receptor-alpha activation via the mitogen-activated protein kinase pathway. Breast Cancer Res 2004;6:R423-36.  Back to cited text no. 18
    



 
 
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