Pregnancy-associated Breast Cancer Research Articles

Abstract PO2-13-05: Deciphering pregnancy-associated breast cancer: distinctive molecular profile and clinical implications from GEICAM/2017-07 EMBARCAM study

Abstract Background: Pregnancy-Associated Breast Cancer (PABC) is defined as BC diagnosed during pregnancy, breastfeeding, or within the first year postpartum. This challenging entity has a distinct biology and worst prognosis and presents an increased risk for metastasis and death compared to non-PABC patients. Identification of molecular pathways that define this malignancy is crucial to explain its biological characteristics and potential association with pregnancy as well as serve to identify new biomarkers with preventive and clinical implications. This study assesses the gene expression profile of a PABC cohort from the Registry Study of Pregnancy and Breast Cancer (GEICAM/2017-07 EMBARCAM study, NCT04603820) to identify distinct molecular signatures and altered pathways for this entity. Methods: This was a multicenter, observational and ambispective age-matched cohort of PABC patients (n=46) and non-PABC patients (n=49). We analyzed the expression of 776 genes involved in 23 key breast cancer pathways, using the nCounter® Breast Cancer 360™ Panel (NanoString Technologies) on BC tumor samples, including molecular subtypes by PAM50 gene signature. Associations between individual differential genes and epidemiological and clinical features of these patients were explored. Normalized differential expression values were log2-transformed for statistical analysis in nSolver Software (NanoString Technologies). P-values were adjusted within each gene/signature and on the grouping variable level difference t-test using the Benjamini and Yekutieli False Discovery Rate (FDR) adjustment. Results: PABC patients’ clinical subtypes were distributed as 43,5% HR-positive/HER2-negative, 17,4% HER2-positive and 39,1% triple negative BC. These patients reported higher family history of BC/ovarian cancer compared to non-PABC (52.17% vs 26.53%; p=0.0124). Differential gene expression showed distinct molecular profiles in PABC and non-PABC patients: significantly genes enrichment involved in cell proliferation and p53 signature for PABC patients and higher expression of apoptosis, TGF-β, and PTEN signatures for non-PABC (adj p< 0.05). Furthermore, CDK4 expression signature (adj p=0.124) and DNA damage repair signatures Homologous Recombination Deficiency (HDR) (adj p=0.083) and BRCAness (adj p=0.220) were also upregulated in PABC tumors. The most significantly upregulated genes in PABC patients (CCNA2, DEPDC1, FAM83D, CDC20, CDKN3, TRIP13, TTK, MAD2L1, KIF2C, and UBE2C) (adj p< 0.05) were involved in cell cycle regulation and DNA damage repair. PABC basal-like tumors were found to be significantly more prevalent than non-PABC, as per the PAM50 classification (45.7% vs 20.4%; p=0.020). Interestingly, basal-like PABC showed higher expression of ESR1 than basal-like non-PABC (logFC=1.486; p=0.022). In contrast, luminal A PABC tumors exhibited lower ESR1 expression vs non-PABC (logFC=-1.5; p=0.021). Additionally, HER2-enriched PABC tumors displayed lower B7-H3/CD276 expression compared to HER2-enriched non-PABC (adj p=0.031). Conclusions: Our study shows that PABC is potentially a clinical and molecular different entity with predominance of the basal-like subtype. Moreover, our results suggest the activation of oncogenic pathways related to cell proliferation, DNA damage repair and p53 mutations which may lead to a clinically more aggressive phenotype for PABC patients. Likewise, the enrichment of BRCAness and HRD signatures found in PABC patients in our study may suggest an increased genetic instability due to a breakdown in the DNA damage repair. These findings may be clinically relevant and translate to new treatment options in PABC patients, who may benefit from therapies targeting DNA repair or cell-cycle checkpoints, such as PARP inhibitors. Citation Format: Juan de la Haba-Rodríguez, Regina Peña, Marina Pollan, Yolanda Jerez Gilarranz, Jose Ponce, Antonio Fernández Aramburu, Blanca Cantos, Ana Santaballa Bertrán, Elena Galve, María Eva Pérez, Susana de la Cruz, María Helena López-Ceballos, Yolanda Fernández, Fernando Moreno, Sonia González, Manuel Ruíz - Borrego, Isabel Blancas, José L Alonso-Romero, Álvaro Jiménez-Arranz, Raúl Rincón, Silvia Guil, Alejandra Díaz-Chacón, Rosalía Caballero, Begoña Bermejo, Angel Guerrero. Deciphering pregnancy-associated breast cancer: distinctive molecular profile and clinical implications from GEICAM/2017-07 EMBARCAM study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-13-05.

Abstract PS13-04: Frequent Intra-Tumoral Hypoxia in Pregnancy-Associated Breast Cancer

Abstract Rationale: Breast cancer is the most common malignancy in pregnant women, occurring in approximately 1:3000 pregnancies. Breast cancer diagnosed during pregnancy or after childbirth is also known as Pregnancy-Associated Breast Cancer (PABC). PABC is known for exhibiting several unfavorable prognostic tumor characteristics, such as an advanced tumor stage at diagnosis, high histologic grade and frequent hormone receptor negativity. Most probably, several interplaying mechanisms may promote the tumor progression and adverse clinical outcome of PABC. One of these mechanisms may be the presence of hypoxia, a relative state of low intra-tumoral oxygen levels which is a known marker of adverse outcome in breast cancer. However, the occurrence and prognostic consequences of the presence of intra-tumoral hypoxia in PABC have not been studied yet. Methods: We constructed a cohort with histopathological, clinical, and outcome data of patients diagnosed with breast cancer during pregnancy (PrBC) or within one year after childbirth (PPBC) in the Netherlands between 1988 and 2022. Next, tissue blocks of all patients were collected from the participating Dutch pathology laboratories. Using H&E stained slides of the tumor tissue blocks, we selected suitable donor sites for a tissue micro array (TMA). Slides from these TMAs were stained for three important hypoxia-associated proteins: glucose transporter-1 (Glut-1), carbonic anhydrase IX (CAIX) and hypoxia-inducible factor-1α (HIF-1α). Expression was scored by an expert breast pathologist blinded by clinicopathologic data. Results: For a total of 195 PrBC and PPBC patients, we were able to assess the expression of Glut-1, CAIX and HIF-1α on tumor cells. Patients had a median age of 33 years at diagnosis, whilst a large majority had a Bloom & Richardson grade III tumor (76%) with frequent hormone receptor negativity (50%). Expression of hypoxia-associated proteins was frequent, with 61% of the tumors expressing Glut-1, 30% expressing CAIX and 56% expressing HIF-1α. In total, 153 (78%) of the tumors expressed at least one of the hypoxia-associated proteins. We observed a significantly worse 5-year overall survival for patients with intra-tumoral hypoxia in comparison to patients without intra-tumoral hypoxia (70% vs. 90%, p=0.046). Conclusions: We show that the presence of intra-tumoral hypoxia in PABC is common, with 78% of tumors expressing at least one of the studied hypoxia-associated proteins. Importantly, patients with tumors overexpressing hypoxia-markers have a significantly worse survival. This shows that intra-tumoral hypoxia may be an important underlying carcinogenic mechanism in PABC, and might be a promising novel therapeutic target in this patient group. Citation Format: Carsten Bakhuis, Carmen Van Dooijeweert, Britt Suelmann, Pieter Westenend, Sabine Linn, Elsken Van der Wall, Paul Van Diest. Frequent Intra-Tumoral Hypoxia in Pregnancy-Associated Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS13-04.

Abstract PS13-01: Worse Prognosis for Breast Cancer in the Second and Third Trimesters and Shortly Postpartum:An Update of the Dutch Pregnancy-Associated Breast Cancer Cohort

Abstract Rationale: Pregnancy-Associated Breast Cancer (PABC), often defined as breast cancer during pregnancy (PrBC) or in the first year postpartum (PPBC), is known for its aggressive histopathology and higher stage at diagnosis. In a previous study of the nationwide Dutch PABC Cohort, we observed an impaired survival for patients diagnosed in the second and third trimester of pregnancy. However, the etiology of these differences, and how this relates to the patients diagnosed with breast cancer in the postpartum period (PPBC) or after an abortion (AABC), remains to be elucidated. While we are exploring the etiologic hypotheses, we updated and expanded our database to compare these specific PABC subgroups. Methods: All pathology reports of invasive breast carcinoma between January 1st 1988 and July 1st 2022 were screened for pregnancy-related keywords to find all patients diagnosed with PrBC, PPBC or AABC within one year after childbirth or an interrupted pregnancy (induced abortion or miscarriage before a gestational age of 24 weeks). A local patient series provided 22 additional cases. Pregnant patients were subdivided by gestational trimester at time of diagnosis. The different PrBC, PPBC and AABC subgroups were compared by histopathology, clinical characteristics and outcome. Results: 787 patients were included, of whom 60% were pregnant during their diagnosis. Median age at diagnosis was 34 years. In line with our previous findings, a large majority (68%) of patients had a Bloom & Richardson (B&R) grade III tumor and 37% of tumors were triple negative. Moreover, over a third of patients presented with lymph node metastases (38%). We observed two distinct groups based on histopathology and prognosis: group A, consisting of three patient groups: (I) patients diagnosed in the first trimester of pregnancy, (II) patients diagnosed between 6-12 months postpartum, and (III) patients diagnosed after an abortion, and group B, consisting of two patient groups, (I) patients diagnosed in the second or third trimester of pregnancy or (II) within 6 months after childbirth. Compared to group A, patients in group B more often had B&R grade III tumors: (73% vs. 60%, p=0.002) and more frequently had triple negative tumors (43% vs. 28% in group A, p< 0,001). Survival was significantly worse for patients in group B (5-year OS 67,3% versus 88.2%, p< 0.001). In a multivariable analysis, corrected for grade, type of surgery and overall stage, these differences upheld with an HR of 1.515 (95% CI 1,012 – 2,268). Conclusions: With this extensive update of our nationwide Dutch PABC cohort, we show that especially PrBC patients diagnosed in the second and third trimesters and PPBC patients within six months after childbirth exhibit unfavorable tumor characteristics, with an associated worse prognosis. This highlights the need for in-depth analyses in these specific groups of PABC patients to elucidate the etiologic mechanisms involved. Citation Format: Carsten Bakhuis, Carmen Van Dooijeweert, Britt Suelmann, Janneke Verloop, Pieter Westenend, Sabine Linn, Paul Van Diest, Elsken Van der Wall. Worse Prognosis for Breast Cancer in the Second and Third Trimesters and Shortly Postpartum:An Update of the Dutch Pregnancy-Associated Breast Cancer Cohort [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS13-01.

Abstract PO4-20-05: An open label phase III randomized trial to evaluate the efficacy of Post-chemotherapy Axillary Conservation Surgery in breast cancer (PACS)

Abstract Background- Axillary lymph nodes (ALN) status is the most important prognostic factor in breast cancer. Traditionally, a complete axillary lymph node dissection (ALND) has been standard of care for those patients who have a positive node pre-chemotherapy. However, lately axillary conservation is paving its way in the post-chemotherapy setting as well to avoid significant morbidity of ALND. Most sentinel node biopsy studies have failed to achieve the desired false negative rate(FNR). (Boughey JC et al, JAMA. 2013 Oct; Kuehn T et al, Lancet Oncol. 2013; Boileau JF et al, J Clin Oncol. 2015 Jan).We previously reported a low FNR of low axillary sampling (LAS) in the post-chemotherapy setting. (Parmar et al, JCO-GO, 2021) We are conducting a phase III, randomised controlled trial of LAS versus complete ALND in post-chemotherapy negative (ypN0) axilla. Aims and objectives- The primary objective is to assess the non-inferiority of LAS in patients who are rendered ypN0 by pre-operative chemotherapy with disease-free survival as primary end point. The secondary objectives are comparing the morbidity of ALND (lymphedema, paraesthesia, and shoulder dysfunction) in the LAS and ALND arms, and to evaluate the impact on overall survival, local, regional, and distant recurrence free survival and quality of life. Trial design- This is a prospective, open label, randomised, phase III trial where histologically proven, non-metastatic, cT1-4,N0-2 breast cancer patients who are rendered ycN0 after pre-operative systemic chemotherapy are being accrued. Patients with prechemo N3 disease, inflammatory breast cancer, recurrent disease, pregnancy associated breast cancer are being excluded from the study. The chemotherapy regimens and surgical assessment is as per standard institutional protocols. After obtaining informed consent, patients undergo LAS during surgery and lymph nodes(LN) are sent for frozen section analysis. If any LN is found to be involved, a complete ALND is carried out. If the staging procedure is negative, then patients are randomised into 2 groups- observation v/s complete ALND. Stratification factors are T stage, N stage, Hormone receptor status, Her2 receptor status and number of chemotherapy cycles taken. Morbidity assessment is done with- Constans shoulder score, arm volumetry, paraesthesia assessment, and a QOL questionnaire- Self-reported Breast cancer Lymphedema Symptom Experience Index (BCLSEI). A baseline assessment pre-surgery is followed by 6 monthly morbidity assessments and regular oncologically relevant follow-up up to 5 years. A two-sided log-rank test with an overall sample size of 2316 with a 10% dropout rate (1158 in ALND and 1158 in LAS group) achieves 80% power at a 0.05 significance level to detect a hazard ratio of 1.16 (upper limit of non-inferiority) when the proportion surviving in the control group is 0.71. An interim analysis will be carried out at 25% events and conditional power will be calculated. If the conditional power is below 20%, then the study will be discontinued for futility. The study has been approved by Institutional Ethics Committee (CTRI/2022/07/044461) Expected Study and Results- We started accrual in February 2023 and have screened 63 and randomized 45 patients until now. Ours is a first large randomised prospective study in the post-chemotherapy axillary management setting which will help us understand the efficacy of axillary conservation surgery in patients who are node negative post neoadjuvant chemotherapy. In future, lesser morbid procedures than LAS like targeted axillary dissection can be tested in the same trial. However, LAS as a technique of axillary conservation suits resource constraints and high volume setting such as ours. Citation Format: Shalaka Joshi, Jessicka Shah, Pallavi Daphale, Rohini Hawaldar, Anuradha Daptardar, Ayushi Sahay, Tanuja Shet, Palak Popat, Tabassum Wadasadawala, Nita Nair, Vani Parmar, Bipin Bandre, Shabina Siddique, Vaibhav Vanmali, Sudeep Gupta, Rajendra Badwe. An open label phase III randomized trial to evaluate the efficacy of Post-chemotherapy Axillary Conservation Surgery in breast cancer (PACS) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-20-05.

Abstract PO2-28-04: Pregnancy-associated relapse of triple-negative breast cancer

Abstract Introduction: Pregnancy Triple-negative breast cancer(TNMC) is the absence of ER PR and HER2 receptor expression. It constitutes about 15-20% of all breast cancers and is known to be the aggressive form with a high relapse rate (1). Interestingly, it usually affects women aged < 40 and has a low survival rate in African-American females. This case is a typical presentation of a 38-year-old young woman with PMH of T2NO right triple-negative breast cancer diagnosed in 2017 s/p right mastectomy with sentinel LN biopsy, received immunotherapy and chemotherapy, has been cancer-free for two years, and developed metastatic cancer during her pregnancy. In this case, we understand the diagnostic and therapeutic challenges of TNBC during pregnancy. Case: A 38-year-old African American woman, G0, T2NO triple negative invasive ductal carcinoma, underwent a right breast mastectomy and sentinel LN biopsy. She received treatment with (Anti-PD-L1 Antibody) concomitant with weekly paclitaxel and Doxorubicin/Cyclophosphamide (AC) chemotherapy. However, she had a residual 4cm tumor for which she was treated with adjuvant therapy with capecitabine for six months. A repeat Mammogram in 2019 showed no evidence of malignancy. In 2021, the patient was G2P2L1, admitted to the hospital after having a seizure. CT reported cystic/necrotic left parietal lesion mass effect with 8mm right-sided midline shift with metastasis to lungs and abdominal wall. She underwent L parietal craniectomy with resection of the tumor. At 32 weeks of gestation , chemotherapy with carboplatin and paclitaxel was given after her C-section and Gamma knife radiosurgery for metastatic lesions. She developed super refractory seizures, was induced into a coma with therapeutically anesthetic agents, and passed eventually. Discussion: Little literature exists on pregnancy-associated relapse of triple-negative breast cancer and its deterioration. Our patient was in remission for two years and was diagnosed with metastatic cancer during her second pregnancy. John et al., (2018) discussed an interesting association between breastfeeding, parity, and occurrence of TNBC, that there is a two-fold increased risk of developing TNBC with high parity(3 full-term pregnancies) and short-term breastfeeding (< 12 months) (2). Studies have also shown that cancers during or postpartum pregnancy are aggressive with more tumor burden and metastasize to the lungs, liver, and brain, which is consistent with our patient. (3) Conclusion: Pregnancy-associated breast cancer is diagnostically and therapeutically challenging during or in the postpartum period and with a high propensity of the triple-negative type. It requires a multidisciplinary team approach, awareness in the African American population, clinical suspicion of breast mass during pregnancy warrants imaging, and prolonged breastfeeding postpartum. Diagnosis is usually delayed due to pregnancy, and more research is needed on the diagnostic modalities during pregnancy for early treatment initiation. References Almansour NM. Triple-Negative Breast Cancer: A Brief Review About Epidemiology, Risk Factors, Signaling Pathways, Treatment and Role of Artificial Intelligence. Front Mol Biosci. 2022 Jan 25;9:836417. doi: 10.3389/fmolb.2022.836417. PMID: 35145999; PMCID: PMC8824427. John EM, Hines LM, Phipps AI, et al. Reproductive history, breast-feeding and risk of triple-negative breast cancer: The Breast Cancer Etiology in Minorities (BEM) study. International Journal of Cancer. 2018;142(11):2273. doi:10.1002/ijc.31258 Amant F, Deckers S, Van Calsteren K, Loibl S, Halaska M, Brepoels L, et al. Breast cancer in pregnancy: recommendations of an international consensus meeting. Eur J Cancer (2010) 46(18):3158–68. 10.1016/j.ejca.2010.09.010 Citation Format: Vaidarshi Abbagoni. Pregnancy-associated relapse of triple-negative breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-28-04.

Abstract PO2-26-06: Prognostic factors pregnancy associated breast cancer: one year versus two years

Abstract Aims: The trend of delayed delivery, the number of women with breast cancer during a pregnancy or in the years after pregnancy is expected to increase Pregnancy breast cancer confers a worse prognostic. Study if the interval pregnancy breast cancer more one year to two years influences the prognostic factors like pregnancy breast cancer one year after Methods: Study 1186 patients with breast cancer and prognostic factors. Analyze delivery before breast cancer, and the interval of last childbirth, one year, more one year to two years and more two years, with prognostic factors (nodes, estrogen receptor, progesterone receptor, HER2 receptor and Ki 67) Results: Breast cancer pregnancy one year after were in 37 patients, more one year to two years in 25 patients and more two years in 491 patients. Positive nodes one year after were in 21 patients, more one year to two year were in seven patients (p < 0'05), and more two years in 155 patients (p=ns). There are not differences (p=ns) in estrogen receptor, progesterone receptor and Ki67, one year versus more one year to two years and more to two years. HER2 and histologic grade there are not differences (p=ns) in one year after versus more one year to two years, but there are differences (p < 0’05) versus more two years Conclusion: Interval last childbirth breast cancer more than one year to two years influences prognostic factors for later breast cancer, and not have differences with prognostic factors than pregnancy one year after Citation Format: Maxim Izquierdo, Sonia Baulies, Carmen Ara, Maria Garcia, Fransec Fargas, Rafael Fabregas, Fransec Tresserra, Pere Barri S. Prognostic factors pregnancy associated breast cancer: one year versus two years [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-26-06.

Breast cancer screening in BRCA1/2 pathogenic sequence variant carriers during pregnancy and lactation

ObjectivesWomen harboring germline BRCA1/BRCA2 pathogenic sequence variants (PSVs) are at an increased risk for breast cancer. There are no established guidelines for screening during pregnancy and lactation in BRCA carriers. The aim of this study was to evaluate the utility of whole-breast ultrasound (US) screening in pregnant and lactating BRCA PSV carriers. MethodsData were retrospectively collected from medical records of BRCA PSV carriers between 2014 and 2020, with follow-up until 2021. Associations between imaging intervals, number of examinations performed and pregnancy-associated breast cancers (PABCs) were examined. PABCs and cancers diagnosed at follow-up were evaluated and characteristics were compared between the two groups. ResultsOverall 212 BRCA PSV carriers were included. Mean age was 33.6 years (SD 3.93, range 25–43 years). During 274 screening periods at pregnancy and lactation, eight (2.9 %) PABCs were diagnosed. An additional eight cancers were diagnosed at follow-up. Three out of eight (37.5 %) PABCs were diagnosed by US, whereas clinical breast examination (n = 3), mammography (n = 1) and MRI (n = 1) accounted for the other PACB diagnoses. One PABC was missed by US. The interval from negative imaging to cancer diagnosis was significantly shorter for PABCs compared with cancers diagnosed at follow-up (3.96 ± 2.14 vs. 11.2 ± 4.46 months, P = 0.002). ConclusionIn conclusion, pregnant BRCA PSV carriers should not delay screening despite challenges like altered breast tissue and hesitancy towards mammography. If no alternatives exist, whole-breast ultrasound can be used. For lactating and postpartum women, a regular screening routine alternating between mammography and MRI is recommended.

Systematic Review of Survival Outcomes of Pregnancy-Associated Breast Cancer in Asian Countries.

Pregnancy-associated breast cancer (PABC) is a rare type of gestational cancer. It poses a significant challenge in diagnosis and management, especially in Asian countries with limited resources. We carried out a systematic literature review and narrative synthesis to identify survival outcomes for women with PABC in Asia. We searched MEDLINE, PubMed, Cochrane Library and the reference lists of the included English language articles for those conducted between January 2010 and August 2022. The search terms were pregnancy-associated breast cancer, breast cancer AND pregnancy, survival of PABC and prognosis of PABC patients. PABC is defined as breast cancer diagnosed either during pregnancy or 1 year-5 years postpartum. This review included observational studies conducted in Asian countries. The final 11 articles met the selection criteria and were analysed. Five of the studies had high quality methods as assessed using the Joanna Briggs Institute (JBI) checklist. We reported study design, year of diagnosis, country, definition of PABC, control group, age of participants, median follow-up time, survival outcomes and pregnancy as prognostic factors. Only five studies reported that PABC patients had a poor overall or disease-free survival rate compared to the control. Pregnancy was a significant independent prognostic factor of breast cancer in only two studies. This review highlights that pregnancy has an unconfirmed association with breast cancer survival in Asia. Most studies that found a non-significant association had small samples, thus there is a need for large-scale multinational epidemiological studies in Asia to establish the survival outcomes in PABC patients.

Impact of Pregnancy on Breast Cancer Features and Prognosis.

pregnancy-associated breast cancer (PABC) affects one in 3000 pregnancies, often presenting with aggressive features. We retrospectively evaluated a cohort of 282 young BC patients (≤45 years old) treated between 1995 and 2019, dividing them into three groups: nulliparous women, women with PABC (diagnosed within 2 years since last pregnancy) and women with BC diagnosed > 2 years since last pregnancy. This last group was further stratified according to the time between pregnancy and BC. The analysis encompassed histological factors (tumor size, histotype, grading, nodal involvement, multifocality, lympho-vascular invasion, hormone receptor expression, Ki-67 index, and HER2 expression), type of surgery and recurrence. Age at diagnosis was younger in nulliparous than in parous women (p < 0.001). No significant differences were noticed regarding histological characteristics and recurrences. At univariate analysis, nodal involvement (OR = 2.4; p < 0.0001), high tumor grade (OR = 2.6; p = 0.01), and lympho-vascular invasion (OR = 2.3; p < 0.05), but not pregnancy (OR = 0.8; p = 0.30), influenced DFS negatively. Multivariate analysis confirmed nodal involvement as the only negative independent prognostic factor for a worse DFS (OR = 2.4; p = 0.0001). in our experience, pregnancy is not an independent adverse prognostic factor for BC DFS.

Survival in pregnancy-associated breast cancer patients compared to non-pregnant controls

BackgroundPregnancy-associated breast cancer (PABC) is a rare entity whose prognosis has previously been studied and is subject to controversy.MethodsSurvival of patients with PABC diagnosed between 2009 and 2021 with breast cancer during pregnancy or until 1 year after childbirth was compared with non-pregnant patients with breast cancer from the same period at La Paz University Hospital. Cox proportional hazards regression was used to compare disease-free (DFS) and overall (OS) survival between the groups, adjusting for grade and pathologic stage.ResultsAmong the 89 included patients with breast cancer, 34 were diagnosed during pregnancy, and 55 were not pregnant. The pregnant patients were more likely to have grade 3 tumors (61.3% vs 37%, p = 0.023) and an advanced stage (pathologic stage III-IV: 44.1% vs 17.6%, p = 0.008). Median follow-up was 47 months for the pregnant group and 46 months for the control group. After adjustments for tumor grade and pathologic stage, OS was comparable between the groups (HR 2.03; 95% CI 0.61 to 6.79; P = 0.25).ConclusionsThe outcome of women diagnosed with PABC is comparable to young non-pregnant controls. However, it should be taken into account that PABC has a more aggressive phenotype.

Abstract 6852: Immune microenvironment profiling of pregnancy associated breast cancer: A transcriptomic and multiplex immunohistochemical analyses

Abstract Background: Pregnancy-associated breast cancer (PABC) is BC diagnosed during pregnancy or within 2 years after pregnancy. Although PABC is a rare subgroup of BC, the outcome of PABC is worse than BC developed in the same age group unrelated to pregnancy. The proliferation and involution of mammary gland during and after pregnancy create a unique immune microenvironment in the breast. Comprehensive profiling of the tumor immune microenvironment in PABC is important but lacking. Methods: We retrospectively identified PABC patients from electronic medical records and their tumor blocks from pathology department in our institution. Age- and stage-matched BC patients were selected as control group. NanoString Breast Cancer 360 Gene Expression panel and Opal Polaris 7 color immunohistochemical (IHC) were utilized to profile PABC from transcriptome and protein levels. Result: PABC (N=26), BC developed 2 years (BC&amp;gt;2Y, N=54) after pregnancy, and matched non-pregnant BC patients (NPBC, N=27) were included in the final analysis respectively. Samples from BC&amp;gt;2Y (remote influence from pregnancy) and NPBC (pregnancy did not contribute to BC) both served as control groups for PABC patients in our study. PAM50 subtyping categorized patients into luminal A(N=42), luminal B(N=26), basal(N=12), and HER2 (N=25) enriched subgroups. In multiplex IHC analysis, CD4+ cells, CD8+ cells, CD20+ cells, and CD68+/CD163+ (M2) cells were all statistically higher in the tumor samples from PABC and BC&amp;gt;2Y than from NPBC. This suggests a potential contribution of pregnancy in the immune microenvironment. In the luminal A subgroup, CD8+ cells, CD20+ cells, and CD68+/CD163+ cells remain statistically higher in the PABC than in the NPBC samples. In NanoString BC360 transcriptomic profiling, immune cell abundance was evaluated from representative gene signatures. Mast cells were significantly lower in the PABC group than in the NPBC group. Cytotoxic T cells are significantly higher both in the PABC and BC&amp;gt;2Y groups than in the NPBC group. Conclusion: We are the first study to profile immune microenvironment using both transcriptomic and IHC methods. Our study is also unique in using NPBC and BC&amp;gt;2Y patients as control groups for PABC patients. CD8+ T cells are statistically higher in PABC patients than in NPBC patients using either transcriptomic profiling or multiplex IHC analysis. M2 macrophages, which promote tumor growth, are abundant in all the PABC and the luminal A PABC samples. Citation Format: I-Chun Chen, Ching-Hsuan Chen, Chia-Lang Hsu, Tzu-Pin Lu, Yen-Shen Lu, Ching-Hung Lin. Immune microenvironment profiling of pregnancy associated breast cancer: A transcriptomic and multiplex immunohistochemical analyses [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6852.

Unveiling the Role of Pregnancy-Associated Plasma Protein A (PAPP-A) in Pregnancy-Associated Breast Cancer: A Comprehensive Review.

Pregnancy-associated breast cancer (PABC) presents unique challenges due to its occurrence during or shortly after pregnancy. Pregnancy-associated plasma protein A (PAPP-A) has emerged as a potential biomarker and regulator in PABC. This comprehensive review examines the role of PAPP-A in PABC, highlighting its involvement in tissue remodeling and cancer progression. Molecular mechanisms linking PAPP-A to breast cancer, including signaling pathways and interactions with other molecules, are explored. The review also discusses the diagnostic and therapeutic implications of PAPP-A dysregulation in PABC, emphasizing the need for further research to elucidate underlying mechanisms and develop targeted therapies. Collaborative efforts among researchers, clinicians, and industry stakeholders are essential for translating findings into clinically relevant interventions to improve outcomes for PABC patients.

MRI of the Lactating Breast.

The breasts undergo marked physiologic changes during lactation that can make conventional imaging evaluation with mammography and US challenging. MRI can be a valuable diagnostic aid to differentiate physiologic and benign processes from malignancy in patients who are lactating. In addition, MRI may allow more accurate delineation of disease involvement than does conventional imaging and assists in locoregional staging, screening of the contralateral breast, assessment of response to neoadjuvant chemotherapy, and surgical planning. Although the American College of Radiology recommends against patients undergoing contrast-enhanced MRI during pregnancy because of fetal safety concerns, contrast-enhanced MRI is safe during lactation. As more women delay childbearing, the incidence of pregnancy-associated breast cancer (PABC) and breast cancer in lactating women beyond the 1st year after pregnancy is increasing. Thus, MRI is increasingly being performed in lactating women for diagnostic evaluation and screening of patients at high risk. PABC is associated with a worse prognosis than that of non-PABCs, with delays in diagnosis contributing to an increased likelihood of advanced-stage disease at diagnosis. Familiarity with the MRI features of the lactating breast and the appearance of various pathologic conditions is essential to avoid diagnostic pitfalls and prevent delays in cancer diagnosis and treatment. The authors review clinical indications for breast MRI during lactation, describe characteristic features of the lactating breast at MRI, and compare MRI features of a spectrum of benign and malignant breast abnormalities. ©RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material. See the invited commentary by Chikarmane in this issue.

Pregnancy-associated breast cancer : a challenging entity

Pregnancy-associated breast cancer : a challenging entity

Rapid cell isolation in breastmilk in a non-clinical setting by a deterministic lateral displacement device and selective water and fat absorption.

Breastmilk is a reliable source of biomarker-containing, sloughed breast cells that have the potential to give valuable health insights to new mothers. Furthermore, known DNA-based markers for pregnancy-associated breast cancer are chemically stable and can be safely stored on a commercially available FTA® Elute Micro (EM) card, which can subsequently be mailed to a testing facility for the cost of a stamp. In theory, this archiving process can be performed by nonprofessionals in very low-resource settings as it simply requires placing a drop of breastmilk on an EM card. Although this level of convenience is paramount for new mothers, the low cell density of breastmilk complicates archiving on an EM card as such commercial products and associated protocols were designed for high-cell density physiological fluids such as blood. In this study, we present the use of a deterministic lateral displacement (DLD) device combined with porous superabsorbent polymers and hydrophobic sponges to achieve simple and low-cost cell enrichment in breastmilk. As the critical separation diameter in a DLD device is more heavily dependent on lithographically controlled pillar layout than fluid or flow properties, our use of DLD microfluidics allowed for the accommodation of both varying viscosities in human breastmilk samples and a varying pressure of actuation resulting from manual, syringe-driven operation. We demonstrate successful cell enrichment (>11×) and a corresponding increase in the DNA concentration of EM card elutions among breastmilk samples processed with our hybrid microfluidic system. As our device achieves sufficiently high cell enrichment in breastmilk samples while only requiring the user to push a syringe for 4 min with reasonable effort, we believe that it has high potential to expand EM card DNA archiving for diagnostic applications with low-cell density physiological fluids and in low-resource settings.

Pregnancy-related breast cancer: 14-year experience in a tertiary institution in Hong Kong

BackgroundThe incidence of pregnancy-associated breast cancer (PABC) is increasing. Its tumor characteristics and overall survival compared with those in nonpregnant patients remain controversial. While there have been suggestions that PABC patients have a 40 % increase in the risk of death compared to non-pregnant patients, other studies suggested similar disease outcomes. This study aims to review our local experience with PABC. MethodsTwenty-eight patients diagnosed with PABC and twenty-eight patients diagnosed at premenopausal age randomly selected by a computer-generated system during the same period were recruited. Background characteristics, tumor features, and survival were compared. ResultsAmong the twenty-eight pregnant patients, seventeen were diagnosed during pregnancy, and eleven were diagnosed in the postpartum period. Compared to the non-pregnant breast cancer patients, they presented with less progesterone receptor-positive tumor (35.7 % vs. 64.2 %, p = 0.03). Although there was no statistically significant difference in tumor size (p = 0.44) and nodal status (p = 0.16), the tumor tended to be larger in size (2.94 +/− 1.82 vs 2.40 +/− 1.69 cm) and with more nodal involvement (35.7 % vs 25.0 %). There was also a trend of delayed presentation to medical attention, with a mean duration of 13.1 weeks in the PABC group and 8.6 weeks in the control group. However, the overall survival did not differ (p = 0.63). ConclusionPABC is increasing in incidence. They tend to have more aggressive features, but overall survival remains similar. A multidisciplinary approach is beneficial for providing the most appropriate care.

Weekly Paclitaxel for Pregnancy Associated Breast Cancer

BackgroundPregnancy associated breast cancer is the most common cancer diagnosed during pregnancy. When chemotherapy is indicated, although it is more common to use anthracycline-based chemotherapy as a first treatment, we suggest weekly paclitaxel as a valid alternative both in the adjuvant and neoadjuvant setting, as this allows for weekly assessment of maternal–fetal well-being and a quicker maternal and fetal bone marrow recovery in cases of unexpected preterm delivery. Patients and methodsWe present a case series of pregnant breast cancer patients treated with weekly paclitaxel between 2016 and 2022. Patient demographics and tumor characteristics, data on management, delivery, and maternal–neonatal outcomes were extrapolated from institutional electronic databases. ResultsEighteen patients underwent weekly paclitaxel for breast cancer during pregnancy (PrBC); 17 were primary diagnoses and 1 was a recurrence. None of the patients had severe adverse reactions to CT. Two cases of preterm prelabour rupture of membranes were reported while in 1 case treatment was stopped due to threatened preterm birth. Two babies were born large for gestational age, 2 were small for gestational age and 2 babies were growth restricted at birth. At a mean follow up of 42.9 months, 1 patient died, 1 patient was diagnosed with disease recurrence and another patient was diagnosed with disease progression. ConclusionWeekly paclitaxel can be safely administered during pregnancy and should be included in the current therapeutic options for PrBC.

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.

Abstract 14569: Chemotherapy in Pregnancy: Assessing the Safety of Adriamycin Administration in Pregnancy Complicated by Breast Cancer

Introduction: Treatment of Pregnancy Associated Breast Cancer (PABC) with radiation and endocrine therapy is challenging due to potential risks to the fetus. Surgical treatment is safe throughout pregnancy, and chemotherapy agents such as anthracyclines are safe during 2 nd and 3 rd trimesters. Case Presentation: A 39-year-old G4P3 female presented at 8 weeks gestation with a twin pregnancy and a right breast mass with bloody nipple discharge. Past medical history was significant for obesity and chronic hypertension. Biopsy of the mass confirmed weakly ER+/PR-/HER2-, node+, stage IIb PABC. After radical mastectomy and axillary lymph node dissection, 4 Adriamycin and Cyclophosphamide (AC) based adjuvant chemotherapy cycles q3 weeks were started at 12 weeks of gestation with a maternal and fetal echocardiogram, brain natriuretic peptide and troponin measurements after each cycle. A baseline echocardiogram revealed cardiomyopathy with an LVEF of 45% and a severely dilated left ventricle. She was New York Heart Association class II at baseline. Carvedilol 6.25 mg BID was started prior to beginning AC and titrated to 12.5 mg BID due to palpitations after 1 st AC cycle. She tolerated 4 AC cycles with no change in EF from baseline, no symptoms of heart failure, and a normal fetal echocardiogram. Weekly Paclitaxel was resumed to complete 12 cycles prior to radiation treatment. She delivered healthy male and female infants at 32 weeks with no complications (M: APGAR 5 and 7; F: APGAR 8 and 7). Postpartum EF decreased to 40%, necessitating titration of carvedilol to 25mg BID and the addition of Sacubitril/Valsartan 24/26 mg BID. Chest pain complaint after delivery prompted evaluation with computed tomography-based angiogram and cardiac magnetic resonance imaging (CMR), ruling out coronary artery disease. Despite this, no evidence of microvascular disease on CMR symptomatic relief was reported on long-acting nitrates. Discussion: This case demonstrates the importance of multidisciplinary patient management, particularly for those with low LVEF who are at higher risk of decompensation. Despite not knowing the etiology of PABC, she could be suffering from thrombotic microangiopathy of small coronary vessels, which explains relief from nitrates.

Pregnancy-associated Breast Cancer: Why Breast Imaging During Pregnancy and Lactation Matters.

Pregnancy-associated breast cancer is characterized as breast cancer diagnosed during pregnancy, within the first postpartum year, or during lactation. It usually presents as a palpable mass, although the large majority of palpable masses during pregnancy are benign. Breast cancer is the most common invasive malignancy diagnosed during pregnancy and lactation, and its incidence is increasing as more women delay childbearing. Understanding the appropriate methods for screening and diagnostic workup of breast findings in this population is imperative for radiologists to promptly diagnose pregnancy-associated breast cancer. Use of available imaging modalities should be tailored to patient-specific factors, with US typically the first-line modality due to patient age and decreased sensitivity of mammography in the setting of lactational changes. This article illustrates the spectrum of imaging appearances of pregnancy-associated breast cancer, the appropriate diagnostic imaging workup, and the unique challenges encountered in evaluation of this patient population.