Pregnancy-associated Breast Cancer Cases Research Articles

Survival probabilities and prognostic factors of pregnancy-associated breast cancer in Malaysian women.

Pregnancy-associated breast cancer (PABC) is a rare cancer. This study aimed to determine the survival probabilities and prognostic factors in patients with PABC. A retrospective cohort study was conducted in two tertiary care hospitals in Kota Bharu. We included all patients with breast cancer who were diagnosed by histopathology while pregnant or within 2 years post-partum from 2001 through 2020. We matched patients with PABC to non-pregnant patients with breast cancer by age and year of diagnosis. The data were analyzed using Cox proportional hazard regression. A total of 35 cases of PABC and 70 non-PABC controls were recruited. The 3-year, 5-year, and 10-year survival probabilities for patients with PABC were 58.6%, 47.54%, and 38.03%, respectively. The patients with PABC had a non-significant difference in survival probabilities compared with non-PABC patients. The significant prognostic factors of PABC were age (adjusted hazard ratio [aHR], 0.91; 95% confidence interval [CI], 0.86-0.96; P=0.001), advanced stage of cancer (aHR, 9.97; 95% CI, 3.96-25.2; P<0.001), and no surgery (aHR, 3.16; 95% CI, 1.01-9.85; P=0.047). Pregnancy was not found to be an independent factor in the prognosis of PABC (aHR, 0.72; 95% CI, 0.39-1.28; P=0.266). Women diagnosed with PABC had similar survival probabilities compared with non-PABC patients. Pregnancy was not an independent prognostic factor for breast cancer. This information can be useful when women with breast cancer are counseled and supported with the option of beginning treatment with pregnancy continuation.

Lapses in breast cancer screening for highly penetrant mutation carriers during pregnancy and lactation.

Screening for breast cancer in highly penetrant mutation carriers during pregnancy and lactation is challenging and consensus guidelines are lacking. This study evaluates the lapse in screening and the interval pregnancy-associated breast cancer rate. A single-institution retrospective cohort study of pregnant and lactating patients with known pathogenic germline mutations was performed. Lapse in screening was defined as the interval between the last screening imaging exam obtained before last menstrual period and the subsequent screening imaging. Out of 685 patients, 42 had 1-3 evaluable pregnancies (54 total - 28 managed in High Risk Breast Clinic and 26 by OB/GYN). Mutations were observed in patients in BRCA1 (49%), BRCA2 (36%), CDH1 (5%), CHEK2 (2%), ATM (2%), NF1 (3%), and MSH2 (3%). The average screening lapse was 25 [19, 30] months for patients followed in the High Risk Clinic versus 32.5 [21, 65.75] months for patients followed with Routine Care (p = 0.035). We identified three cases of pregnancy-associated breast cancer (interval cancer rate 6%). Patients with highly penetrant mutations are at risk for the development of interval pregnancy-associated breast cancer. Development of consistent screening guidelines and adherence to those guidelines is needed for this patient population.

Abstract 4914: Pregnancy and breast cancer outcomes

Abstract Background: Pregnancy-associated breast cancer (PABC) poses a unique challenge as hormonal changes occurring in pregnancy potentially interact with breast cancer outcomes. However, reports on prognosis of PABC have been rare and inconsistent, and most of these studies were from Western countries with only few from Asia. We investigated the outcome of PABC linking a large hospital-based database and the nationwide claims database of Korea. Patients and methods: We retrospectively studied a cohort of 3687 female patients of reproductive age (&amp;lt;50 years old) who had undergone surgery for breast cancer at Seoul National University Hospital from 2008 to 2015. Data on stage distribution and tumor characteristics were reviewed from the institutional database, and history of delivery or abortion from the nationwide claims database of Korea for comprehensive identification. Breast cancer during pregnancy was defined as delivery within 9 months of the diagnosis of breast cancer, and postpartum breast cancer as breast cancer diagnosis within 12 months of delivery, with both being counted as PABC. Results: Among 3687 patients, 18 and 45 patients were classified as having breast cancer during pregnancy and postpartum breast cancer, respectively, comprising 63 cases of PABC. Patients with PABC were significantly more likely to have advanced stage and/or hormone receptor negative tumor, and be younger than 35 years old at diagnosis of breast cancer than those without it (P value for T stage, .0001; N stage, .0011; ER negativity, &amp;lt;.0001; PR negativity, &amp;lt;.0001; age at breast cancer diagnosis &amp;lt;35, &amp;lt;.0001). Similar distribution pattern of clinical characteristics was observed with postpartum breast cancer compared to their counterparts (P value for T stage, &amp;lt;.0001; N stage, .0001; M stage, .0421; ER negativity, &amp;lt;.0001; PR negativity, &amp;lt;.0001; age at breast cancer diagnosis &amp;lt;35, &amp;lt;.0001), whereas these characteristics were comparable between patients with and without breast cancer during pregnancy. PABC and postpartum breast cancer were seemingly associated with worse survival with univariate hazard ratio (HR) of 4.53 (95% confidence interval, CI, 2.53-8.13; P value &amp;lt;.0001) and 5.34 (95% CI, 2.91-9.82; P value &amp;lt;.0001), multivariate HR of 1.52 (95% CI, .82-2.83; P value .1841) and 1.57 (95% CI, .82-2.99; P value .1708), respectively. Breast cancer during pregnancy was not associated with worse survival. Conclusions: PABC and postpartum breast cancer tended to be associated with higher stage, hormone receptor negativity, and thus worse survival, but breast cancer during pregnancy had no adverse effect on survival in patients with breast cancer. Note: This abstract was not presented at the meeting. Citation Format: Mihong Choi, Jiyeon Han, Bo Ram Yang, Myoung-jin Jang, Miso Kim, Tae-Yong Kim, Seock-Ah Im, Han-Byoel Lee, Hyeong-Gon Moon, Wonshik Han, Dong-Young Noh, Kyung-Hun Lee. Pregnancy and breast cancer outcomes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4914.

Abstract P4-10-11: Pregnancy-associated breast cancer in a contemporary cohort of newly diagnosed women

Abstract Introduction: Pregnancy-associated breast cancer (PABC) refers to breast cancer (BC) diagnosed during pregnancy, lactation, or in the postpartum period. There is evidence that PABC is associated with a poorer prognosis, and that the development of the disease is influenced by the unique hormonal milieu of pregnancy. The purpose of this study was to investigate the clinicopathologic characteristics associated with PABC in a contemporary cohort of women with newly diagnosed BC. Methods: Our institutional Breast Cancer Database was queried for women diagnosed with breast cancer between 2010-17 who had at least one full term pregnancy (FTP). Variables of interest included patient demographics and clinical and tumor characteristics. PABC was defined as breast cancer diagnosed within 24 months of delivery. Statistical analyses included Pearson's chi-square and logistic regression. Results: Out of a total of 1934 women, 42 (2.2%) had PABC. Median follow up in the total cohort was 4.5 years. After adjusting for age at diagnosis, PABC was associated with older age at first FTP, ethnic minority status, BRCA mutation carriers, presentation with a palpable mass, higher histologic grade, and ER-negative and triple negative receptor status. Variables that were not significantly different between PABC and non-PABC cases included tumor histology, multifocality, presence of lymphovascular invasion, and family history of breast cancer. Table:Selected Characteristics of Women with PABCVariableNon-PABC (n=1892)PABC (n=42)P-value*Age at first full term pregnancy &amp;lt;0.001&amp;lt;35 years1610 (85%)28 (66.7%) ≥35 years277 (15%)14 (33.3%) Race 0.001White1397 (73.8%)23 (54.8%) Black181 (9.6%)8 (19%) Asian175 (9.2%)10 (23.8%) Hispanic131 (6.9%)1 (2.4%) Other8 (0.4%)0 (0%) BRCA 1,2 Positive56 (3%)9 (21.4%)&amp;lt;0.001Method of Presentation 0.002Breast Exam579 (30.6%)30 (71.4%) Mammography1137 (60.1%)10 (23.8%) Ultrasound87 (1.6%)2 (4.8%) MRI67 (3.5%)0 (0%) Other22 (1.2%)0 (0%) Invasive Grade 0.014Low213 (15%)0 (0%) Intermediate763 (53.8%)12 (37.5%) High442 (31.2%)20 (62.5%) Estrogen Receptor 0.034Positive1572 (83.9%)29 (69%) Negative301 (16.1%)13 (31%) Triple Negative135 (7.1%)7 (16.7%)0.041*P-values are age-adjusted. Conclusions: The association of PABC with ethnic minority status in our cohort is interesting and may be reflected in the increased proportion of triple negative breast cancers in the PABC group. In our contemporary cohort, PABC was associated with older age at first FTP. As more women delay childbearing, risk for PABC may increase. Our findings suggest that women who become pregnant at older ages should be followed carefully during pregnancy and in the postpartum period, especially if they are BRCA mutation carriers. The optimal approach for monitoring older women during pregnancy and the postpartum period is unclear. Clinical breast exam may play an important role, especially for those women known to be at increased risk for breast cancer. Citation Format: Gooch JC, Chun J, Jubas T, Guth A, Schnabel F. Pregnancy-associated breast cancer in a contemporary cohort of newly diagnosed women [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-10-11.

Diagnostic pathways and management in women with pregnancy-associated breast cancer (PABC): no evidence of treatment delays following a first healthcare contact

BackgroundWomen with pregnancy-associated breast cancer (PABC), i.e. diagnosed during or within 2 years of pregnancy, have a poor prognosis. We compared symptoms, diagnostics, treatments, and waiting times from first symptoms to treatment initiation in women diagnosed with PABC and non-PABC.Materials and methodsWomen diagnosed with PABC and non-PABC at ages 15–44 were identified in Swedish healthcare registers. Chart information was retrieved for 546 women (273 PABC cases and 273 age- and hospital-matched non-PABC controls) treated at 11 hospitals across Sweden between 1992 and 2009. Distributions of symptoms, diagnostics and treatments were compared. Median waiting times from initial symptoms to start of treatment, and time periods within, were estimated from Kaplan–Meier curves.ResultsInitial symptoms in women with PABC and non-PABC were similar. Women with PABC more often underwent biopsy and ultrasound than mammography at initial examination. Compared to non-PABC, rates of mastectomy and axillary clearance were higher in women with PABC, while endocrine treatment was less common. The time from symptoms to first healthcare contact was non-significantly longer in women diagnosed during or within 6 months of pregnancy. Waiting times from contact with healthcare to diagnosis and treatment were shorter or similar in women with PABC compared to women with non-PABC.ConclusionsThese findings do not support the notion that diagnostic and treatment delays following a first healthcare contact are more common in women diagnosed with breast cancer during or shortly after pregnancy. However, there was some evidence of delays in seeking healthcare among pregnant and lactating women.

Neonatal outcomes of pregnancy‐associated breast cancer: Population‐based study on 11 million births

As the age at first pregnancy continues to rise in the United States so does the incidence of breast cancer diagnosed during pregnancy. Our objective was to evaluate temporal trends in the incidence of pregnancy-associated breast cancer (PABC) and to measure neonatal outcomes associated with PABC. We conducted a population-based cohort study using the 1999-2012 Healthcare Cost and Utilization Project-Nationwide Inpatient Sample (HCUP-NIS) from the United States. Logistic regression models, adjusted for maternal baseline characteristics, examined the effect of PABC on neonatal outcomes. There were 11846300 deliveries between 1999 and 2012, of which 772 cases of PABC were identified, resulting in an overall incidence of 6.5 cases/100000 pregnancies. There was a significant increase in the incidence of PABC during the study period (P<0.05). Women with PABC tended to be older, of white ethnicity, belong to a higher income quartile and to be treated in an urban teaching hospital. In pregnancies complicated by breast cancer, there was a greater risk of preterm delivery (OR 4.84, 95% CI 4.05-5.79) and preterm premature rupture of membranes (OR 1.79, 95% CI 1.06-3.05). No associations were observed between PABC and intrauterine growth restriction, congenital anomalies or intrauterine fetal demise. There is an uptrend in the incidence of PABC and therefore, the need for counseling these patients is also increasing. Although pregnancies with the diagnosis of maternal breast cancer are more prone to premature births, it is encouraging that these babies do not appear to be at increased risk for congenital anomalies, growth restriction, or fetal demise.

Breast cancer during pregnancy: results of maternal and perinatal outcomes in a single institution and systematic review of the literature

To compare the maternal and the perinatal variables of the patients with pregnancy associated breast cancer (PABC) and the pregnant patients without breast cancer (PNABC), we retrospectively included 13 PABC cases and 66.265 PNABC patients. The PABC patients presented a lower mean gestational age at their delivery and had higher induction of labour and prematurity rates. A diagnosis was performed before stage III in 77% of the cases. The overall survival was 90%; moreover, we collected 16 manuscripts when gathering data from 1581 patients with PABC. The mean follow-up time was 70 ± 8 months. The mean maternal age at diagnosis was 34 years old. Most of the patients were at their second trimester of pregnancy. The gestational age at delivery was 35 weeks. A mastectomy was the most frequently used surgical approach. PABC should be managed by a multidisciplinary team, ensuring there is a rigorous oncological treatment, with foetal well-being.IMPACT STATEMENTWhat is already known on this subject? The malignant breast tumours diagnosed during pregnancy, or 1 year after a delivery are increasing, there is evidence supporting the treatment during a pregnancy with maternal and foetal safety. A PABC should be managed by a multidisciplinary team in a referral centre, ensuring that there is a rigorous oncological treatment with foetal well-being.What do the results of this study add? Our results show that the PABC patients in our centre had a mean maternal age older than the PNABC women, as well as a higher percentage of the induction of labour and prematurity. 48 Cancer was usually diagnosed in early stages, and the most common type was ductal infiltrating, with positive hormonal receptors. For those patients continuing their pregnancies, a mastectomy plus a lymphadenectomy was the most frequent chemotherapy, and was usually administered in the third trimester of pregnancy.What are the implications of these findings for future clinical practice and/or further research? Moreover, the number of publications concerning PABC has grown, series are still scarce. We understand the limitations of the low number of the cases on our population, but this study is the first which compare the PABC with the PNABC patients, allowing to describe and compare the obstetrical and perinatal variables. Finally, we consider it is of a paramount importance to create an international database to register in a prospective way all of the cases of PABC to increase our knowledge in this field.

232P - Pregnancy associated breast cancer spotlights

Background: Pregnancy associated breast cancer (PABC) is a rare entity of breast cancer. It is defined as breast cancer occurring during pregnancy or within 12 months from end of pregnancy. Though rare, it represents a very challenging situation to both the physician and patient. This retrospective study is an attempt to focus on PABC cases presenting at our institute regarding their personal, disease characteristics and type of treatment received. Methods: This is a retrospective study conducted at Kasr-Al-Ainy oncology center “NEMROCK”. The files of female patients diagnosed with breast cancer under the age of 40 in the period from January 2005 to December 2014 were retrospectively reviewed. A comparison has been conducted between PABC cases and non-pregnant cases concerning personal and disease characteristics, modality of treatment and outcomes. Results: This study included a total of 175 patients 40 years old or younger, among them 40 were PABC cases. Twenty five percent of PABC presented with distant metastasis at first presentation while only 11.6% of the non-pregnant patients presented with metastasis (P value 0.039). Time from onset of symptoms till breast cancer diagnosis was more than 6 months in 55.6% of PABC cases in comparison to 36.3% in non-pregnant cases (P value 0.043). Concerning treatment; 32.4% of PABC cases received neoadjuvant chemotherapy while 20.7% of non-pregnant patients received it (P value 0.027). There was no statistical difference in personal and disease characteristics between pregnant and non-pregnant patients including family history, pathological subtypes, stage, grade and biological subtypes. There was no statistically significant difference in disease free survival between PABC cases and non-pregnant ones (P value 0.497). Conclusions: PABC is associated with a late diagnosis. Although PABC patients present at later stages than non-pregnant ones and the use of neoadjuvant treatment is higher in pregnant cases, the outcome of patients with PABC is comparable to that of non-PABC of matched age. Legal entity responsible for the study: Kasr alainy department of oncology Funding: None Disclosure: All authors have declared no conflicts of interest.

Breast Cancer and Pregnancy: Experience of Maternity and Neonatology Center of Tunis-Tunisia

Objectives: This document aims to identify the clinical, therapeutic, and prognostic features of this association and to provide the up-to-date management. Methods and materials: Our study design is retrospective based on 25 cases of pregnancy-associated breast cancer, carried out at the Maternity and Neonatology Center of Tunis over a period of 10 years, between January 2001 and December 2013. Results: The mean age of the patients was 35.84 years. Breast cancer was diagnosed during pregnancy in fourteen patients and after delivery in eleven patients. Pathohistological diagnosis was established by ultrasoundguided biopsy and surgical biopsy in fourteen and seven patients, respectively. The most common histological type was infiltrating ductal carcinoma (96% of cases). Pregnancy was completed in nine patients. The mean gestational age at which delivery occurred was 35.4 weeks. Twenty patients underwent surgical treatment by mastectomy and breast-conserving surgery (lumpectomy) associated with axillary lymph node dissection was performed in three cases. Chemotherapy was allowed during pregnancy, and was given to 23 patients. On the other hand, radiotherapy, antiestrogens (Tamoxifene) and targeted therapies (Herceptin) must be postponed after delivery because of their teratogenic effects. After a 5-year follow-up, two of eighteen patients died and six were lost to follow-up. Conclusion: The poor prognosis of the pregnancy-associated breast cancer is no longer attributed to pregnancy but rather to the young age of the patients and the delay in the diagnosis of cancer. Treatment should be started promptly during pregnancy.

Stat3 modulates chloride channel accessory protein expression in normal and neoplastic mammary tissue

Mammary gland regression at the cessation of lactation (involution) is an exquisitely orchestrated process of cell death and tissue remodelling in which Stat3 signalling has an essential role. The involution microenvironment of the mammary gland is considered to be pro-tumourigenic and a proportion of cases of pregnancy-associated breast cancer are suggested to originate in tandem with involution. However, the apparent paradox that STAT3 is required for cell death in normal mammary gland, but is associated with breast cancer cell survival, has not been resolved. Herein, we investigate Stat3-mediated regulation of expression of members of the calcium-activated chloride channel regulator (CLCA) family of proteins during involution and mammary carcinogenesis. Using the conditionally immortal mammary epithelial cell line KIM-2, together with mice exhibiting mammary epithelial cell-specific deletion of Stat3 during lactation, we demonstrate that expression of mCLCA1 and mCLCA2 is elevated in concert with activation of Stat3. By contrast, murine CLCA5 (mCLCA5), the murine orthologue of human CLCA2, is significantly upregulated at 24, 72 and 96 h of involution in Stat3 knockout mice, suggesting a reciprocal regulation of these proteins by Stat3 in vivo. Interestingly, orthotopic tumours arising from transplantation of 4T1 murine mammary tumour cells exhibit both phosphorylated Stat3 and mCLCA5 expression. However, we demonstrate that expression is highly compartmentalized to distinct subpopulations of cells, and that Stat3 retains a suppressive effect on mCLCA5 expression in 4T1 tumour cells. These findings enhance our understanding of the regulation of CLCA channel expression both in vitro and in vivo, and in particular, demonstrate that expression of mCLCA1 and mCLCA2 during involution is profoundly dependent upon Stat3, whereas the relationship between mCLCA5 and Stat3 activity is reciprocal and restricted to different subpopulations of cells.

Abstract P5-08-21: Expression of EZH2 and its downstream effectors pEZH2 and H3K27 in pregnancy associated breast cancer (PABC)

Abstract Background: Pregnancy associated breast cancer (PABC) arises during or after pregnancy, is typically triple negative, and is associated with a poor prognosis. Enhancer of Zeste Homolog 2 (EZH2), a core protein of the polycomb-repressive complex, plays a vital role in the epigenetic maintenance of histone H3 lysine (H3K27) repressive chromatin mark and has been found to be aberrantly expressed in various cancers including the breast. EZH2 is involved in stem cell renewal and is involved the initiation, progression and maintenance of cancer cells. EZH2 has been reported to be highly expressed in triple negative breast cancers and to be associated with poor prognosis. In this study, we assessed expression of EZH2 and its downstream markers phosphorylated EZH2 (pEZH2) and H3K27 and correlated their expression with clinicopathologic characteristics in this aggressive type of breast carcinoma. Design: 23 patients diagnosed with PABC within 2 years of pregnancy (mean age=35.8, range=26-48) and control age-/stage-matched nulliparous women (mean age=37.5, range=29-51) were evaluated. Slides were reviewed and pathologic tumor characteristics were noted. Immunohistochemical stains for EZH2, pEZH2, H3K27 and the cancer stem cell marker ALDH1 were performed on 23 PABC and 15 control cases. Extent (1=1-25% positive tumor cells, 2=26-50%, 3=51-75% or 4=76-100%) and intensity (1=weak, 2=moderate or 3=strong) of staining were assessed. A composite score (CS) was calculated by multiplying the extent by intensity (range=0-9; weak=1-3; moderate=4-6 and strong=7-9). Results: PABCs were more likely than controls to have moderate to strong immunoreactivity for EZH2 (69.6% vs. 33.3%, p=0.04). All PABC and control cases expressed EZH2 and pEZH2, while 60.9% of PABC and 40% of control cases expressed H3K27. Within the PABC group, moderate to strong EZH2 expression was seen more frequently in grade 3 tumors (86.7% in grade 3 tumors vs. 37.5% in grades 1-2, p=0.03). Of interest, all triple negative (TN) PABC cases had moderate to strong EZH2 (100% vs. 43.8%, p=0.02). All five PABC cases with the strongest EZH2 (CS=9) were grade 3 tumors (3 TN, 1 HER2+ and 1 luminal B), 60% of which had positive lymph node metastasis. Although 83.3% of ALDH1+ cases also had moderate to strong EZH2, no significant correlation was observed. Conclusions: 1. PABCs express EZH2 and pEZH2 consistently. 2. PABCs are more likely than controls to have moderate to strong immunoreactivity for EZH2. 3. Within the PABC group, all triple negative tumors and the majority of grade 3 tumors have high EZH2 expression. 4. PABC cases with the strongest EZH2 are grade 3 tumors that have positive lymph nodes. Increased expression of EZH2 in PABC may contribute to the poor prognosis in these cases. Our findings add to the understanding of the molecular pathways that operate in different subtypes of breast carcinomas. Citation Format: Blanco Jr LZ, Parini V, Dhamne SA, Siziopikou KP. Expression of EZH2 and its downstream effectors pEZH2 and H3K27 in pregnancy associated breast cancer (PABC). [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-08-21.

Abstract P1-07-01: Characteristics, treatment and outcomes of breast cancer diagnosed during pregnancy and the year after delivery

Abstract Background: Pregnancy associated breast cancer (PABC) is defined as breast cancer (BC) diagnosed during pregnancy or during the year after delivery. Whether PABC is associated with inferior outcomes compared to non-PABC is uncertain. Data suggests characteristics and outcomes of BC diagnosed during pregnancy and BC diagnosed within the year after delivery may differ. However, most previous research has not separated BC cases diagnosed during pregnancy from those diagnosed within the year after delivery. Methods: We performed a single institution retrospective cohort study of women diagnosed at the Johns Hopkins Hospital with PABC between 1985-2014 and matched controls. Women with BC diagnosed during pregnancy and BC diagnosed during the year after delivery formed two separate case groups. Controls were matched 2:1 to each of the cases by time period of diagnosis, age (+/- 5 years) and extent of disease at diagnosis. Clinicopathologic features, treatment and outcomes were compared between each case group and its respective controls. Univariate Cox modeling stratified by matching set was used to compare time to relapse between cases and their matched controls. Results: Of 140 PABC cases identified, BC was diagnosed during pregnancy in 65 and during the year after delivery in 75. 135 controls were matched to the cases diagnosed during pregnancy and 145 controls were matched to the cases diagnosed during the year after delivery. Compared to their controls, cases diagnosed after delivery were more likely to have grade 3 tumors (81% versus 60%) and less likely to be hormone receptor (HR)-positive (62% versus 82%). Similarly, compared to their controls, cases who were pregnant at diagnosis were more likely to have grade 3 tumors (77% versus 57%) and less likely to be HR-positive (54% versus 75%). The frequency of HER2-positivity between cases diagnosed during pregnancy or during the year after delivery was similar to their respective control groups. A higher proportion of cases diagnosed during pregnancy underwent mastectomy than their controls, but this was not statistically significant (74% versus 67%). Most patients in both case groups and both control groups received chemotherapy. The proportions of patients in both case groups compared to their controls who received radiation were similar. Rates of relapse were high in the entire study population. There was a non-significant increased risk of relapse for both the cases diagnosed during pregnancy compared to their controls (HR 1.77, 95% CI 0.844-3.73, p 0.13) and for the cases diagnosed after delivery compared to their controls (HR 1.51, 95% CI 0.70-3.24, p 0.30). Conclusions: In our study population, women diagnosed with BC during pregnancy or within the year after delivery were more likely to have high grade and HR-negative disease than controls matched for age, extent of disease and time period of diagnosis. Rates of recurrence were high among our young study population. Findings must be interpreted with caution due to small sample size, but suggest that rates of relapse were not significantly higher among the cases diagnosed during pregnancy or within the year after delivery compared to their controls. Citation Format: O'Sullivan CC, Wang Z, Zhang Z, Umbricht C, Jeter SC, Rosner GL, Stearns V, Smith KL. Characteristics, treatment and outcomes of breast cancer diagnosed during pregnancy and the year after delivery. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-07-01.

Breast cancer in pregnancy: an institutional experience.

BackgroundBreast cancer is one of the most common cancers diagnosed during pregnancy. Pregnancy-associated breast cancer (PABC) is defined as breast cancer diagnosed during pregnancy or within 12 months of delivery. Nowadays PABC can be safely diagnosed, staged, and treated during pregnancy with good outcomes for both the mother and the fetus. Recent studies suggest that prognosis of women diagnosed during postpartum seems to be worse. In order to gain a better understanding of the PABC, we reviewed our centre’s experience.Patients and methodsWe assessed the clinicopathological parameters, evolution, and outcome of patients treated in the Fundación Instituto Valenciano de Oncología of Valencia, Spain, from October 1990 to October 2013, and compared the results of patients diagnosed during pregnancy (group ‘A’) and patients diagnosed within one year of delivery (group ‘B’).Of 12,000 cases of breast cancer registered in our database, 35 cases of PABC were identified. We included 11 patients in group ‘A’ and 24 in group ‘B’.ResultsIn our group the median age was 35 years (range 29–42), of which ten (28%) patients had family history (first grade) of breast cancer, four patients were BRCA 1 mutation carriers. Axillary node compromise was found in 19 patients (53.5%), 24 patients were stage II or III at diagnosis (68.5%), 22 (62.8%) were ER positive, and nine (25.7%) were HER-2 positive.In group A (n = 11), five patients diagnosed before 18th week decided that a therapeutic abortion be performed before treatment, two patients were treated during pregnancy, one with chemotherapy without treatment associated complications during delivery. Four women diagnosed after 28th week decided to delay the treatment until delivery.After a follow up of 172 months, the relapse free survival (RFS) was 69% at five years and 45% at ten years. Overall survival (OS) at five years was 90.8% and 74.2% at ten years for all patients. For group ‘A’ OS was higher with 90% at five years versus 80% in group ‘B’. The differences between the groups were not statistically significant p = 0.368.ConclusionIn our experience, there is a higher OS in patients diagnosed during pregnancy suggesting a better prognosis for this group of women but the difference between the groups is not statistically significant. Our study is limited because of our small sample.

Pregnancy associated breast cancer: an institutional experience.

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. 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). 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. 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.

Contemporary multidisciplinary treatment of pregnancy-associated breast cancer

Breast cancer diagnosed during pregnancy poses unique challenges. Application of standard treatment algorithms is limited by lack of level I evidence from randomized trials. This study describes contemporary multidisciplinary treatment of pregnancy-associated breast cancer (PABC) in an academic setting and explores early maternal and fetal outcomes. A search of the Dana-Farber/Harvard Cancer Center clinical databases was performed to identify PABC cases. Sociodemographic, disease, pregnancy, and treatment information, as well as data on short-term maternal and fetal outcomes, were collected through retrospective chart review. 74 patients were identified, the majority with early-stage breast cancer. Most (73.5%) underwent surgical resection during pregnancy, including 40% with sentinel lymph node biopsy and 32% with immediate reconstruction. A total of 36 patients received anthracycline-based chemotherapy during pregnancy; of those, almost 20% were on a dose-dense schedule and 8.3% also received paclitaxel. 68 patients delivered liveborn infants; over half were delivered preterm (< 37 weeks), most scheduled to allow further maternal cancer therapy. For the infants with available data, all had normal Apgar scores and over 90% had birth weight >10th percentile. The rate of fetal malformations (4.4%) was not different than expected population rate. Within a multidisciplinary academic setting, PABC treatment followed contemporary algorithms without apparent increase in maternal or fetal adverse outcomes. A considerable number of preterm deliveries were observed, the majority planned to facilitate cancer therapy. Continued attention to maternal and fetal outcomes after PABC is required to determine the benefit of this delivery strategy.

Does Pregnancy-Associated Breast Cancer Imply a Worse Prognosis? A Matched Case-Case Study

Background: Significant controversy exists in the literature regarding the role of pregnancy in the prognosis of breast cancer. We designed a matched case-case study, matching pregnancy-associated breast cancer (PABC) cases with breast cancer cases for stage, age, and year of diagnosis. Patients and Methods: 39 consecutive cases of PABC were matched with 39 premenopausal cases of breast cancer. Univariate and multivariate survival analyses followed by adjustment for stage, grade, estrogen receptor status, and age at diagnosis, were performed. Results: Regarding overall survival (OS), univariate analysis pointed to longer OS in non-PABC cases vs. PABC cases. Accordingly, a more advanced stage predicted shorter survival. In the multivariate analysis, the independent aggravating effect mediated by pregnancy persisted. Interestingly, a post hoc nested analysis within PABC cases indicated that the 3rd trimester pointed to shorter OS. The aforementioned results on OS were also replicated during the examination of relapse-free survival. Conclusion: Implementing a matched case-case design, the present study points to pregnancy as a poor prognostic factor for breast cancer.

P2-01-04: The Post-Partum Diagnosis of Pregnancy Associated Breast Cancer Confers an Increased Risk for Metastasis without Increased Incidence of Poorer Prognosis Biologic Subtype.

Abstract Background: All women who complete a childbirth have an increased risk for the subsequent breast cancer regardless of age at their first birth. In younger women, this period truncates 10 years later and pregnancy then becomes protective, whereas in older mothers the risk persists. Moreover, breast cancers diagnosed subsequent to a recent childbirth have an increased risk for metastasis and death. However much of the existing data is confounded by inclusion of cases diagnosed during pregnancy. Hypothesis: Our preclinical models of pregnancy associated breast cancer (PABC) has identified the “involution hypothesis”, where the normal physiologic post-partum breast involution is the pregnancy-related event promotional of breast cancer growth, invasion and metastasis. We have performed a retrospective cohort study, restricted to postpartum PABC and controls, to fully characterize post-partum PABC by biologic subtype and known predictors for metastasis. Also we identify if the specific period of post-partum PABC has a higher risk for metastasis then non-PABC, as predicted by our animal model studies. Methods: We performed a retrospective cohort of 527 cases of breast cancer diagnosed at age 45 or younger from 1981–2011. Pregnancy status was identified from medical records and defined as nulliparous (n=107), PABC (up to 5 years post-partum of last childbirth, n=114), and Later Parous (&amp;gt;10 years post-partum, n=239). Clinicopathologic characteristics were obtained from pathology records. Outcomes data obtained through the University of Colorado Tumor Registrar. Hazard ratios of risk of metastatic recurrence of nulliparous and PABC groups were analyzed using a Cox Proportional Hazards Model and time to metastatic recurrence was analyzed using standard Kaplan Meier curves. Results: Compared to nulliparous cases, PABC cases were more frequently Stage IV(11.4% v. 4.9%), T3 tumor size(17.3% v. 13.1%), poorly differentiated(56.6% v. 49.0%), lobular histology(4.5% v.1.0%), with lymphovascular invasion(30.4% v. 24.5%) and with involved lymphnodes(57.6% v. 48.6%). No differences were seen between Luminal A, Luminal B, Her 2 and Triple Negative subtypes. Average follow-up was 3.4 years for nulliparous, 3.5 for PABC and 4.6 for Later Parous. Survival analysis revealed a cumulative 5-year metastatic recurrence free probability of 80.6% for nulliparous, 68.5% for PABC and 80.5% for Later Parous. Compared to nulliparous, PABC had greater than a three times higher risk for subsequent metastatic recurrence (HR 3.29, 95% CI: 1.25−8.63). No significant difference in the risk of metastatic recurrence for Later Parous compared to nulliparous was observed (HR: 1.079, 95% CI: 0.46−2.55). Conclusion: Post-partum PABC is characterized by higher stage at diagnosis but without enrichment for poorer prognosis biologic subtypes. Post-Partum PABC has an increased risk for metastasis within five years of diagnosis, with an overall 3.29 times higher risk of a metastatic recurrence. These data support our hypothesis that the post-partum window, and the associated role of naturally occurring involution, may be promotional of tumor growth, invasion and metastasis as previously identified in our animal models. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-01-04.

Current or recent pregnancy is associated with adverse pathologic features but not impaired survival in early breast cancer

Pregnancy-associated breast cancer (PABC) may be defined as breast cancer diagnosed during pregnancy or within 1 year of giving birth. Conflicting data exist regarding the impact of pregnancy on clinical features and prognosis of breast cancer. A single-institution retrospective chart review was performed of 99 patients identified with PABC between 1992 and 2007. Non-PABC controls were matched 2:1 to PABC cases by year of diagnosis and age. The differences in clinical features were compared between cases and controls using chi-square tests. Univariate and multivariate analyses were performed to assess the effect of PABC on survival. Of the 99 PABC cases, breast cancer was diagnosed during pregnancy in 36 patients, and after delivery in 63. PABC cases were more likely than controls to be negative for estrogen receptor (59% vs 31%, P < .0001) and negative for progesterone receptor (72% vs 40%, P < .0001). Cases were also more likely to have advanced T class (P = .0271) and N class (P = .0104) and higher grade tumors (P = .0115). With a median follow-up of 6.3 years for cases and 4.7 years for controls, overall survival did not differ between cases and controls (P = .0787). On multivariate analysis, the independent prognostic factors for overall survival were estrogen receptor status (P = .0031) and N class (P = .0003). The diagnosis of PABC was not an independent prognostic factor (P = .1317). PABC is associated with more adverse tumor features than non-PABC matched for age and year of diagnosis. After correcting for pathologic features, the diagnosis of PABC is not in itself an adverse prognostic factor for survival.

Hidden malignant cells within leukocyte aggregates: Seeds for invasive and metastatic cancer?

Background: Our previous studies revealed that leukocyte infiltration into aged or injured myoepithelial cell layers is a key trigger for breast tumor invasion and metastasis. Our current study further assessed the possibility that leukocyte aggregates may harbor detached individual tumor cell or clusters of tumor cells. Materials and methods: Tissue sections from patients with pregnancy-associated breast cancer (PABC) and controls were subjected to morphological and immunohistochemical assessment with a panel of leukocyte and tumor cell related markers. Results: A total of 63 leukocyte aggregates were detected in the 20 PABC cases studied. Of these, 55 (87%) were distributed within normal or hyperplastic lobules adjacent to invasive lesions. Over 70% of these leukocyte aggregates harbored detached individual tumor cell or cell clusters with malignant properties, including strong p53 positivity, elevated proliferation, reduced cell surface adhesion molecules, and cytological resemblance to adjacent invasive cancer cells. A significant number of these tumor cells or condensed chromosomes of mitotic tumor cells were observed to conjoin with the plasma membrane of leukocytes. Similar alterations were seen in leukocyte aggregates within the inter-lobular space and in non-PABC with a lower frequency. Conclusions: These findings suggest that leukocyte infiltration may trigger dissemination of tumor cells from their primary site, and that leukocyte aggregates may serve as a reservoir for disseminated tumor cells that may be physically dragged to distant sites by leukocytes during their migration.

Abstract P3-11-10: Risk Factors for Pregnancy-Associated Breast Cancer: A Report from the Nigerian Breast Cancer Study

Abstract Background: It is known that pregnancy has a dual effect on breast cancer risk, with increased risk of breast cancer in short term and decreased risk in the long run. Pregnancy-associated breast cancer (PABC), occurring during pregnancy and several years postpartum, has poor prognosis and is challenging in clinical management. However, risk factors for PABC, except for pregnancy per se, are less understood. Other reproductive factors including age at menarche and age at first live birth may play important roles in the development of PABC. Methods: The study is based on the Nigerian Breast Cancer Study, a case-control study of breast cancer conducted in Ibadan, Nigeria, between 1998 and 2009. In-person interviews were conducted using structured questionnaires to collect detailed epidemiologic data. Pre-menopausal women who were 50 years old or younger were eligible to this analysis. The breast cancer cases were divided in two groups: PABC (diagnosed during pregnancy or within 5 years postpartum) and non-PABC. Polytomous logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CI), contrasting each group of cases versus controls. Age in 3-year category, ethnicity, education, family history of breast cancer, history of benign breast disease, hormonal contraceptive use, alcohol drinking, height, and body mass index were adjusted in the multivariate models. Results: In total, 1440 women were eligible to this study, including 311 PABC cases, 357 non-PABC cases, and 772 healthy controls. In the multivariate analysis adjusting aforementioned potential confounders, age at menarche was inversely associated with non-PABC (p=0.002, Table 1) but only trend towards significance for PABC (p=0.12). Age at first live birth was associated with lower risk of non-PABC but was associated with elevated risk of PABC. Table 1. Odds ratios and 95% confidence intervals for PABC and non-PABC Conclusions: We found menarche at older age may be protective against all premenopausal breast cancer, but age at first live birth has different role in the development of pregnancy-associated breast cancer and other premenopausal breast cancer in Nigerian women. The findings suggest that the trend towards delayed child-bearing may increase in the occurrence of breast cancer complicated by pregnancy. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-11-10.