ABSTRACT
BACKGROUND: Little is known about the treatment of breast cancer during pregnancy. We aimed to determine whether treatment for breast cancer during pregnancy is safe for both mother and child. METHODS: We recruited patients from seven European countries with a primary diagnosis of breast cancer during pregnancy; data were collected retrospectively if the patient was diagnosed before April, 2003 (when the registry began), or prospectively thereafter, irrespective of the outcome of pregnancy and the type and timing of treatment. The primary endpoint was fetal health for up to 4 weeks after delivery. The registry is ongoing. The study is registered with ClinicalTrials.gov, number NCT00196833. FINDINGS: From April, 2003, to December, 2011, 447 patients were registered, 413 of whom had early breast cancer. Median age was 33 years (range 22-51). At the time of diagnosis, median gestational age was 24 weeks (range 5-40). 197 (48%) of 413 women received chemotherapy during pregnancy with a median of four cycles (range one to eight). 178 received an anthracycline, 15 received cyclophosphamide, methotrexate, and fluorouracil, and 14 received a taxane. Birthweight was affected by chemotherapy exposure after adjustment for gestational age (p=0·018), but not by number of chemotherapy cycles (p=0·71). No statistical difference between the two groups was observed for premature deliveries before the 37th week of gestation. 40 (10%) of 386 infants had side-effects, malformations, or new-born complications; these events were more common in infants born before the 37th week of gestation than they were in infants born in the 37th week or later (31 [16%] of 191 infants vs nine [5%] of 195 infants; p=0·0002). In infants for whom maternal treatment was known, adverse events were more common in those who received chemotherapy in utero compared with those who were not exposed (31 [15%] of 203 vs seven [4%] of 170 infants; p=0·00045). Two infants died; both were exposed to chemotherapy and delivered prematurely, but both deaths were thought not to be related to treatment. Median disease-free survival for women with early breast cancer was 70·6 months (95% CI 62·1-105·5) in women starting chemotherapy during pregnancy and 94·4 months (lower 95% CI 64·4; upper 95% CI not yet reached) in women starting chemotherapy after delivery (unadjusted hazard ratio 1·13 [95% CI 0·76-1·69]; p=0·539). INTERPRETATION: Although our data show that infants exposed to chemotherapy in utero had a lower birthweight at gestational age than did those who were unexposed, and had more complications, these differences were not clinically significant and, since none of the infants was exposed to chemotherapy in the first trimester, were most likely related to premature delivery. Delay of cancer treatment did not significantly affect disease-free survival for mothers with early breast cancer. Because preterm birth was strongly associated with adverse events, a full-term delivery seems to be of paramount importance. FUNDING: BANSS Foundation, Biedenkopf, Germany and the Belgian Cancer Plan, Ministry of Health, Belgium.
Subject(s)
Abnormalities, Drug-Induced/epidemiology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Birth Weight/drug effects , Breast Neoplasms/drug therapy , Infant, Newborn, Diseases/chemically induced , Infant, Newborn, Diseases/epidemiology , Pregnancy Outcome/epidemiology , Adult , Apgar Score , Breast Neoplasms/diagnosis , Breast Neoplasms/pathology , Breast Neoplasms/surgery , Carcinoma, Ductal/diagnosis , Carcinoma, Ductal/drug therapy , Carcinoma, Ductal/pathology , Carcinoma, Ductal/secondary , Carcinoma, Lobular/diagnosis , Carcinoma, Lobular/drug therapy , Carcinoma, Lobular/pathology , Carcinoma, Lobular/secondary , Carcinoma, Lobular/surgery , Cohort Studies , Delivery, Obstetric/statistics & numerical data , Disease-Free Survival , Europe , Female , Humans , Incidence , Infant, Newborn , Lymphatic Metastasis , Male , Middle Aged , Multivariate Analysis , Neoplasm Staging , Organ Preservation , Pregnancy , Pregnancy Complications, Neoplastic/drug therapy , Registries , Retrospective Studies , Young AdultABSTRACT
PURPOSE: We aimed to determine the prognosis of patients with breast cancer diagnosed during pregnancy (BCP). PATIENTS AND METHODS: In this cohort study, a multicentric registry of patients with BCP (from Cancer in Pregnancy, Leuven, Belgium, and GBG 29/BIG 02-03) compiled pro- and retrospectively between 2003 and 2011 was compared with patients who did not have associated pregnancies, using an age limit of 45 years. Patients with a diagnosis postpartum were excluded. The main analysis was performed using Cox proportional hazards regression of disease-free survival (DFS) and overall survival (OS) on exposure (pregnant or not), adjusting for age, stage, grade, hormone receptor status, human epidermal growth factor 2 status, histology, type of chemotherapy, use of trastuzumab, radiotherapy, and hormone therapy. RESULTS: The registry contained 447 women with BCP, mainly originating from Germany and Belgium, of whom 311 (69.6%) were eligible for analysis. The nonpregnant group consisted of 865 women. Median age was 33 years for the pregnant and 41 years for the nonpregnant patients. Median follow-up was 61 months. The hazard ratio of pregnancy was 1.34 (95% CI, 0.93 to 1.91; P = .14) for DFS and 1.19 (95% CI, 0.73 to 1.93; P = .51) for OS. Cox regression estimated that the 5-year DFS rate for pregnant patients would have increased from 65% to 71% if these patients had not been pregnant. Likewise, the 5-year OS rate would have increased from 78% to 81%. CONCLUSION: The results show similar OS for patients diagnosed with BCP compared with nonpregnant patients. This information is important when patients are counseled and supports the option to start treatment with continuation of pregnancy.
Subject(s)
Breast Neoplasms/mortality , Breast Neoplasms/pathology , Cause of Death , Pregnancy Complications, Neoplastic/diagnosis , Pregnancy Complications, Neoplastic/mortality , Adult , Belgium , Biopsy, Needle , Breast Neoplasms/therapy , Cohort Studies , Combined Modality Therapy/methods , Confidence Intervals , Disease-Free Survival , Female , Germany , Humans , Immunohistochemistry , Kaplan-Meier Estimate , Middle Aged , Pregnancy , Pregnancy Complications, Neoplastic/therapy , Prognosis , Proportional Hazards Models , Reference Values , Registries , Retrospective Studies , Risk Assessment , Survival Analysis , Treatment OutcomeABSTRACT
BACKGROUND: The presence of sex steroid receptors in breast cancer tissue is of considerable diagnostic/prognostic value. However, the relative utility of the diverse assays used for receptor detection/quantitation is disputed. We compared the utility of a monoclonal antibody-based semiquantitative immunohistochemical assay of estrogen receptor alpha (irERalpha) and of quantitative single-point radioligand assays of "cytosolic" estrogen (ERc) and progesterone receptors (PRc). MATERIAL/METHODS: Correlations were studied between the receptor levels in 235 breast cancers in patients treated between 1987 and 1990. Relationships were then analyzed between tumor receptor status, overall survival (OS; end-point: 10 years postmastectomy), age, axillary nodal status, and adjuvant tamoxifen in primary breast cancer patients for whom the respective data were accessible (N < or =121). RESULTS: Univariate analysis showed no correlation between OS and the ERc status, whereas positive irERalpha status was a favorable (p<0.05) prognosticator for the 5-year follow-up, and positive PRc status for the 10-year follow-up. Lymph node-positive patients who received adjuvant tamoxifen (2 x 10 mg/day) for a minimum of 12 months had significantly longer OS than those who did not receive the treatment. Multivariate regression of Cox proportional risk showed significance of axillary metastases, adjuvant tamoxifen, and ER status, but not of age and PRc status as independent prognosticators of OS. CONCLUSIONS: These results show the prognostic utility of the PRc radioligand assay, a slight prognostic advantage of the irERalpha assay over the radioligand ERc assay, and stress the importance of adjuvant antiestrogen therapy for overall survival in node-positive primary breast cancer patients.