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Breast Cancer Diagnosed During Pregnancy

Breast Cancer Diagnosed During Pregnancy

ANTICANCER RESEARCH 27: 1705-1708 (2007)

Breast Diagnosed during

BARBARA BODNER-ADLER, KLAUS BODNER and HARALD ZEISLER

Department of Obstetrics and Gynecology, University of Vienna Medical School, Vienna, Austria

Abstract. Cancer is rare during pregnancy, but cancer during pregnancy or within one year of delivery. Breast is the second most common cancer in pregnant women. cancer diagnosed during pregnancy is often discovered at a Pregnancy-associated breast cancer (PABC) is defined as breast late stage but it is not clear whether this pattern relates to cancer that occurs during pregnancy or within one year of diagnostic delay or accelerated growth owing to increased delivery. Five cases of PABC occurring during the second and vascularity, hormonal exposure, or suppression of the third trimester of pregnancy managed at the University Hospital immune system during pregnancy (3). of Vienna during the year 2005/2006 are reported. A review of The goals of breast cancer treatment, such as local the available literature is also presented. Five patients were control of the disease and the prevention of systemic diagnosed with PABC which was detected in completely different metastases, are the same in a pregnant as in a weeks of pregnancy. In two women, the diagnosis was made non-pregnant woman, but some modifications may be during the second trimester of pregnancy and in three during the necessary to minimize fetal harm. Breast and chest wall third trimester. The treatment depended, among other things, on irradiation for example are postponed until after delivery the gestational age at diagnosis. The patients diagnosed during because of the risks of fetal exposure to (4). The the second trimester received six courses of neoadjuvant need for prompt therapy often presents a clinical dilemma type FEC (5-, epirubicin, cyclo- of considerable magnitude as there is always a conflict phosphamide). Locoregional radiotherapy and were between optimal maternal therapy and the resultant risks postponed until after delivery. The three patients diagnosed imposed on fetal well-being. As breast cancer diagnosed during the third trimester received adequate therapy after during pregnancy is more frequently locally advanced at delivery. The mean age of the patients at the time of diagnosis presentation than breast cancer in non-pregnant patients, was 37 years (range: 33-40 years) and all patients were neoadjuvant or primary systemic chemotherapy may be diagnosed at an advanced stage. All patients were alive and free appropriate during pregnancy (5). Five cases of breast of symptoms and signs at the time of writing. All infants are cancer diagnosed during pregnancy and managed at the healthy and no congenital malformation or stillbirth was University Hospital of Vienna between June 2005 and observed. In conclusion, late diagnosis and poor prognosis of June 2006 are reported. A discussion of the available PABC are common in literature. Ttreatment options seem to be literature is also presented. reduced in pregnant women and mainly depend on the patient’s condition as well as on the gestational age at presentation. In a Patients, Methods and Results multidisciplinary approach, an optimal therapy schedule should be assessed depending on these two conditions. The mean age of the patients at the time of diagnosis was 37 years (range: 33-40 years). Breast cancer was detected in Breast cancer in pregnancy is rare with an of completely different weeks of pregnancy. In two women 1:3,000 to 1:10,000 and is the second most common cancer diagnosis was made during the second trimester of type after (1, 2). Pregnancy-associated breast pregnancy and in three during the third trimester. The cancer (PABC) is defined as breast cancer that occurs treatment depended, among other things, on the gestational age at the time of diagnosis. Patients diagnosed around the second trimester normally received six courses of neoadjuvant chemotherapy with 5-fluorouracil, epirubicin Correspondence to: Barbara Bodner-Adler, MD, Department of and (FEC) during pregnancy, but Gynecology and Obstetrics, University of Vienna Medical School, locoregional radiotherapy and surgery were usually A-1090 Vienna, Währinger Gürtel 18-20, Austria. Tel: +43 1 postponed until after delivery. The patients who were 40400 2962, Fax:+43 1 40400 2911, e-mail: Barbara.Bodner- [email protected] diagnosed during the third trimester received therapy (surgery, chemotherapy, irradiation) after delivery. All five Key Words: Pregnancy, breast cancer, risk factors. patients presented with an advanced stage at the time of

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Table I. Histopathology and immunohistochemistry of the patients. Table II. Clinicopathological and obstetric characteristics of the patients with breast cancer. Case Histopathology Stage ER PR HER2 MIB Case 1 Inflammatory T4b, neg pos pos neg 50% 12345 invasive, lobular N4a G 3 Maternal age, years 33 40 40 40 37

2 Invasive, ductal T2 neg neg neg pos 80% Gestational age G 3 N0 at diagnosis, weeks 26 16 22 32 34 Therapy during pregnancy yes yes yes no no 3 Invasive, lobular T3 pos pos neg neg Mode of delivery C/S spontan. C/S C/S C/S G3 N0 Gestational age at delivery 36 38 36 35 37 Infant birth weight (g) 2920 2940 2530 2380 3570 4 Invasive, ductal T1c neg neg neg pos APGAR score G 3 NOS at 1 minute <7 0 0 0 0 0

5 Mucinous T2 pos neg neg neg at 5 minutes <7 0 0 0 0 0 G 2 N0 Cord pH <7.1 0 0 0 0 0

ER: ; PR: receptor; HER 2: human spontan.: spontaneous; C/S: cesarean section; APGAR: activity, pulse, epidermal receptor; p53: tumor suppressor; MIB-1: grimace, appearence, respiration – calculated by the neonatologist 1, 5 proliferation index; pos: positive; neg: negative. and 10 minutes after birth.

diagnosis. The exact histopathology as well as the Patients treated only after pregnancy. Case four presented clinicopathologic parameters of the patients are presented with a left side, T1c, N1a, low grade breast cancer at a in Tables I and II. gestational age of 32 weeks. A with SLND was performed after delivery and an adjuvant hormonal therapy Patients treated during pregnancy. The first patient presented as well as locoregional radiotherapy was started after with a bilateral breast cancer (T4d, N4a on the right; T3, N4a surgery. on the left) at a gestational age of 26 weeks. Both tumors Case five presented with a left side, T2, N0, low grade were of low grade. The patient was treated with three courses breast cancer diagnosed at a gestational age of 34 weeks. Six of neoadjuvant FEC chemotherapy. After cesarean section, cycles of neoadjuvant ET chemotherapy were started and she was first treated with three courses of neoadjuvant lumpectomy and dissection was performed, where etoposide (ET) chemotherapy and then had a bilateral 1 out of 22 lymph nodes was positive. Locoregional and lymphonodectomy, followed by adjuvant radiotherapy and hormonal therapy with Nolvadex were Taxol and Herceptin chemotherapy and irradiation therapy. started after surgery. The second patient presented with a left side, low grade All patients were alive and free of symptoms and signs at breast cancer (T2, N0) at a gestational age of 16 weeks. Six the time of writing. courses of neoadjuvant FEC chemotherapy were administered and a lumpectomy with Obstetric and neonatal outcome. All five women had normal dissection (SLND) was performed during pregnancy. The single with normal fetal development. No sentinel lymph node was successfully identified and was congenital malformation, stillbirth or intrauterine growth without any evidence of disease. Locoregional radiotherapy restrictions were observed in fetuses whose mothers was administered after delivery. received chemotherapy during pregnancy. The third patient presented with a low grade, right side The mode of delivery was mainly cesarean section at 35 breast cancer (T3, N0). Four courses of FEC neoadjuvant to 37 weeks of pregnancy under general and chemotherapy were administered during pregnancy. After tracheal intubation. One patient delivered spontaneously at delivery, neoadjuvant chemotherapy was completed with 38 weeks of gestation. two more cycles FEC. Following two attempts at The APGAR scores (activity, pulse, grimace, appearence, conservative surgery, a mastectomy was necessary. respiration – calculated by the neonatologist 1, 5, and 10 Hormonal therapy with Nolvadex (to continue for five minutes after birth) and cord pH of all infants were in the years) was also implemented. normal range.

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Discussion In conclusion, late diagnosis and poor prognosis of PABC is confirmed by our observation in which advanced maternal Physiological changes during pregnancy and lactation, due age at the time of diagnosis was also common. In a to increased levels, result in an increase in multidisciplinary approach, an optimal therapy schedule breast volume and firmness. These changes make clinical should be assessed depending on these two conditions. and radiological detection and evaluation of breast masses difficult (4). It is possible that the increased hormone References levels during pregnancy also accelerate the growth of any existing tumors, after transformation from premalignant 1 Anderson JM: Mammary and pregnancy. B Med J 1: to malignant breast cells has been triggered (7). PABC 1124-1127, 1979. 2 White TT: Prognosis of breast cancer for pregnant and nursing has long been regarded as having a poor prognosis, with women: analysis of 1413 cases. Surg Gynecol Obstet 100: 661- the earliest reports describing 5-year survival rates of 666, 1955. <20%, and the outlook for PABC is less favorable than 3 Woo JC, Yu T and Hurd TC: Breast cancer in pregnancy. A that for non-pregnant women with breast cancer (8). The literature review. Arch Surg 138: 91-98, 2003. poor prognosis was thought to be partly explained by a 4 Yang WT, Dryden MJ, Gwyn K, Whitman GJ and Theriault R: tendency for pregnant patients to present at a more Imaging of breast cancer diagnosed and treated with advanced stage than non-pregnant women, possibly chemotherapy during pregnancy. 10: 1148, 2006. 5 Bonnier P, Romain S, Dilhuydy JM et al: Influence of reflecting delay in diagnosis (5, 9). The patients with pregnancy on the outcome of breast cancer: a case control PABC in this report also presented with advanced stage study. Int J cancer 72: 720-727, 1997. at the time of diagnosis. Some authors have also proposed 6 Eedarapalli P and Jain S: Breast cancer in pregnancy. J Obstet that pregnancy itself may be an independent predictor of Gynecol 26(1): 1-4, 2006. worse survival (5). 7 Albrektsen G, Heuch I, Thoresen ST and Kvale G: Clinical Additionally, the cases in the present report were all at stage of breast cancer by parity, age at birth, and time since an advanced maternal age at the time of diagnosis, as the birth: a progressive effect of pregnancy ? Cancer Epidemiol Prev 15: 65-69, 2006. mean age of our patients was 37 years. 8 Otake M, Schull WJ and LEE S: Threshold for radiation- Chemotherapy has been more widely used in the second related severe mental retardation in prenatally exposed A-bomb and third trimesters, as organogenesis is completed and fetal survivors: a re-analysis. Int J Radiat Biol 70: 755-763, 1996. malformations are therefore unlikely to occur (10). Only one 9 Ishida T, Yokoe T, Kasumi et al: Clinicopathologic characteristics prospective study was found, from the M.D. Anderson and prognosis of breast cancer patients associated with pregnancy Cancer Center, in which 24 women were treated with and lactation: analysis of case-control study in Japan. Jpn J , cyclophosphamide and 5-fluorouracil for Cancer Res 83: 1143-1149, 1992. 10 Ring AE, Smith IE and Ellis PA: Breast cancer and pregnancy. primary or recurrent breast cancer. No detectable congenital Annals Oncol 16: 1855-1860, 2005. anomalies or fetal deaths were observed (11). 11 Berry DL, Theriault RL, Holmes FA et al: Management of Three of our patients received FEC chemotherapy during breast cancer during pregnancy using a standardized protocol. J pregnancy due to early gestational age at the time of Clin Oncol 17: 855-861, 1999. diagnosis. Their three infants were healthy and no congenital malformation or intrauterine growth retardations were Received December 14, 2006 observed after short term follow-up. Birth weight, APGAR Revised March 6, 2007 score and cord pH were also in the normal range. Accepted March 9, 2007

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