Postpartum Breast Research Articles

Effect of Wangbuliuxing combined with massage on breastfeeding and lactation function in cesarean section women

To explore the effect of Wangbuliuxing (semen vaccariae) combined with massage at breast and acupoint on breastfeeding and lactation function in cesarean section women. A total of 120 cases of cesarean section women were randomly divided into an observation group and a control group, 60 cases in each group. The control group was treated with routine nursing. On the basis of the control group, the observation group was treated with oral administration of Wangbuliuxing decoction, twice a day for 7 days; in addition, massage at breast and acupoint (Zhongfu [LU 1], Yunmen [LU 2], Danzhong [CV 17], 2 min per acupoint per time) was given, twice a day for 7 days. The onset time of lactation, 48-hour postpartum lactation volume, breast swelling and pain, 42-day postpartum breastfeeding were compared between the two groups; the serum levels of prolactin at 48 and 72 h after delivery were measured, and the body mass of newborns at birth and 42 d after delivery were recorded. The onset time of lactation in the observation group was earlier than that in the control group (P<0.05), the 48-hour postpartum lactation volume was higher than the control group (P<0.05), and the breast swelling pain 48 h after delivery was lighter than the control group (P<0.05). Forty-two days after delivery, the success rate of breastfeeding in the observation group was 91.7% (55/60), which was higher than 76.7% (46/60) in the control group (P<0.05). At 48 and 72 h after delivery, the level of serum prolactin in the observation group was higher than that in the control group (P<0.05). On 42 d after delivery, the body mass of newborns in the two groups was higher than that at birth (P<0.05), and that in the observation group was higher than the control group (P<0.05). Wangbuliuxing combined with massage at acupoint and breast could significantly shorten the onset time of lactation, improve the lactation volume, effectively improve breast swelling and pain, increase breastfeeding rate and promote the growth and development of newborns.

Postpartum breast cancer has a distinct molecular profile that predicts poor outcomes

Young women’s breast cancer (YWBC) has poor prognosis and known interactions with parity. Women diagnosed within 5–10 years of childbirth, defined as postpartum breast cancer (PPBC), have poorer prognosis compared to age, stage, and biologic subtype-matched nulliparous patients. Genomic differences that explain this poor prognosis remain unknown. In this study, using RNA expression data from clinically matched estrogen receptor positive (ER+) cases (n = 16), we observe that ER+ YWBC can be differentiated based on a postpartum or nulliparous diagnosis. The gene expression signatures of PPBC are consistent with increased cell cycle, T-cell activation and reduced estrogen receptor and TP53 signaling. When applied to a large YWBC cohort, these signatures for ER+ PPBC associate with significantly reduced 15-year survival rates in high compared to low expressing cases. Cumulatively these results provide evidence that PPBC is a unique entity within YWBC with poor prognostic phenotypes.

Observation of Intervention Effect of Postpartum Breast Nursing on Promotion of Breast Feeding and Prevention of Postpartum Milk Siltation

Observation of Intervention Effect of Postpartum Breast Nursing on Promotion of Breast Feeding and Prevention of Postpartum Milk Siltation

HUBUNGAN TINGKAT PENGETAHUAN IBU NIFAS DENGAN PERILAKU PERAWATAN PAYUDARA DALAM MENCEGAH BENDUNGAN ASI DI WILAYAH KERJA PUSKESMAS MASAT KABUPATEN

A person's knowledge about an object contains two aspects, namely positive aspects and negative aspects. These two aspects will determine a person's attitude; the more positive aspects of the object known, the more positive the attitude towards a particular object (Wawan 2014). An initial survey conducted by researchers on postpartum women in the working area of the Masat Community Health Centre, South Bengkulu Regency, found that of the 10 postpartum women met, 5 did not know how to take care of their breasts, and of the five mothers, 3 experienced breast milk diarrhoea during the breastfeeding period. The purpose of this study was to determine the relationship between the level of knowledge of postpartum women and breast care behaviour in preventing breast milk dams in the Masat Health Centre working area, South Bengkulu Regency. This research design was of the quantitative analytic type with a cross-sectional approach. The population of this study was all postpartum women starting immediately after delivery and continuing up to 6 weeks in the Masat Health Centre working area with a sample of 40 people. Data analysis was done with the chi-square test. The results showed that most of the postpartum women had poor knowledge, namely 15 people (37.5%), and most of the postpartum women did not do breast care, namely 23 people (57.5%). The value of 2 count (8.3) &gt; 2 table (5.591) and the value of (0.015) (0.05) There is a relationship between the knowledge of postpartum women and breast care behaviour to prevent breast milk dam in the working area of Masat Health Centre, South Bengkulu Regency.

Clinical outcomes and prognostic biomarkers among pregnant, post-partum and nulliparous women with breast cancer: a prospective cohort study.

To compare clinical-pathologic characteristics and outcomes of pregnancy-associated, post-partum (PP) and nulliparous (NP) breast cancer (BC) patients and explore mediators of the poor prognosis associated with post-partum BC. A prospective database of 233 women ≤ 40years of age diagnosed with BC between February 2008 and January 2015 was analysed. Clinical-pathologic characteristics and outcomes among pregnant, PP and NP patients were compared using chi-square or Kruskal-Wallis tests. The Kaplan-Meier method was used to estimate disease-free survival (DFS), distant DFS and overall survival (OS). Survival curves were compared using the log-rank test. Univariable Cox proportional hazards regression models were used to evaluate factors that were potentially prognostic for the clinical outcomes of interest; a multivariable Cox model was constructed using a forward stepwise selection process. Androgen receptor (AR), GATA3, PDL1 status and the presence/absence of tumour-infiltrating lymphocytes (TILs) were assessed when possible. Pre-treatment neutrophil and lymphocyte counts were abstracted retrospectively. Statistical significance was defined as a p value ≤ 0.05. Women ≤ 2years PP had a numerically higher incidence of lymph node-positive and high-grade disease and were significantly more likely to have estrogen receptor-negative BC compared to NP controls. With a median follow-up of 7.2years, increasingly poor outcomes were observed among NP (longest OS), > 2years PP, ≤ 2years PP and pregnant (shortest OS) patients, but these differences were not statistically significant. The ≤ 2years PP group had significantly lower AR expression, a strong trend toward higher PDL1 expression and a higher expression of stromal TILs compared to NP women. PPBC patients had numerically lower DFS and OS compared to NP controls. Higher PDL1 and stromal TILs in PPBC suggest that adjuvant immunotherapy may be effective in the post-partum BC subgroup.

Breast cancer diagnosed in the post-weaning period is indicative for a poor outcome

BackgroundIn young women, a breast cancer diagnosis after childbirth increases the risk for metastasis and death. Studies in rodents suggest that post-weaning mammary gland involution contributes to the poor prognosis of postpartum breast cancers. However, this association has not been investigated in humans, mainly because of missing information on the patient's lactation status at diagnosis. Patients and methodsClinicopathological data of 1180 young women with primary invasive breast cancer, diagnosed within 2 years postpartum (PP-BC), during pregnancy (Pr-BC), or nulliparous (NP-BC), were collected. For PP-BC patients, breastfeeding history was retrieved to differentiate breast cancers identified during lactation (PP-BCDL) from those diagnosed post-weaning (PP-BCPW). Differences in prognostic parameters, first site of distant metastasis, and risks for metastasis and death were determined between patient groups. ResultsCox proportional hazard models pointed to a twofold increased the risk of metastasis and death in PP-BCPW patients compared with PP-BCDL (hazard ratio [HR] 2.1 [PDRS = 0.021] and 2.9 [POS = 0.004]), Pr-BC (HR 2.1 [PDRS<0.001] and 2.3 [POS<0.001]) and NP-BC (HR 2.1 [PDRS<0.001] and 2.0 [POS<0.001]) patients. Prognosis was poorest for PP-BCPW patients who did not breastfeed or only for ≤ 3 months before diagnosis. This could not fully be attributed to differences in standard prognostic characteristics. In addition, PP-BCPW tumours showed a 3- to 8-fold increased risk to metastasise to the liver, yet this did not correlate with the poor outcome of this patient cohort. ConclusionsBreast cancer diagnosed shortly after weaning specifically adds to the poor prognosis in women diagnosed with PP-BC. Apart from the importance of an increased awareness, these data show that detailed lactation data need to be registered when breast cancer outcome in young women is investigated.

Abstract 790: A Utah Population Data Base Study of young women's breast cancer outcomes by parity status

Abstract Importance: A diagnosis of breast cancer after childbirth is reported to increase risk for metastasis and death in patients ≤45 years of age. Data to discern if a postpartum diagnosis is an independent risk factor for poor outcomes remain limited. Objective: Determine associations between time since last pregnancy and time to metastasis and breast cancer-specific death using cases available from the Utah Population Data Base (UPDB). Secondary objectives are time to metastasis and breast cancer specific-death delineated by tumor stage and ER status. Study Design: This is a population-based study of 2,977 women with stage I, II, or III breast cancer (BC) diagnosed at ≤ 45 years of age from 1996 to 2017. The study population was identified from the UPDB, a statewide dynamic database of linked data received from the Utah SEER Cancer Registry, birth certificates, death certificates, and medical records. Clinical prognostic factors include patient age at diagnosis, year of diagnosis, tumor size, stage, and estrogen receptor (ER) status. The primary exposures are no prior childbirth or time between the most recent childbirth and a breast cancer diagnosis, and primary outcomes are distant metastasis-free survival and breast cancer specific death. Results: Among the 2,977 predominantly white women from the state of Utah, USA, the reproductive histories of the breast cancer patients were grouped as nulliparous (n = 867), and parous: diagnosed 0-5 years (n = 614), &amp;gt;5-10 years (n = 615) and &amp;gt;10 years (n = 881) since last childbirth. We find a breast cancer diagnosis within 5 years of childbirth is associated with elevated risk for metastasis after controlling for diagnosis year, diagnosis age, tumor stage, and ER status [HR (95% CI) =1.64 (1.16, 2.32)], particularly in Stage I/II disease [HR (95% CI) =1.89 (1.24, 2.87)]. The 0-5 year group also had elevated risk of breast cancer-specific death [HR (95% CI) =1.57 (1.07, 2.32)]. While ER-negative tumors were enriched in women diagnosed 0-5 years postpartum, this enrichment could be attributed largely to the younger age of this reproductive group. Further, postpartum breast cancer patients diagnosed with ER-positive disease within 5 years of a completed pregnancy had significantly worse distant metastasis-free survival than nulliparous patients with ER-negative disease. Conclusions: In this population level study from the state of Utah, a diagnosis of breast cancer within 5 years postpartum is a risk factor for metastasis and breast cancer-specific death that is independent of known clinical parameters, including ER status. The increased risk for poor outcomes is highest in stage I/II diagnoses. Relevance: For women with breast cancers classically considered as having good prognostic tumor features, i.e. stage I or II and ER-positive, a postpartum diagnosis is a dominant demographic feature of increased risk for metastasis and death. Citation Format: Pepper Schedin, Sonali Jindal, Solange Bassale, Zhenzhen Zhang, Alison Fraser, Emily Guinto, Virginia F. Borges, Motomi Mori, Ken R. Smith. A Utah Population Data Base Study of young women's breast cancer outcomes by parity status [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 790.

Abstract 2672: Semaphorin 7a promotes cellular transformation via activation of pro-survival signaling

Abstract We seek to further our understanding of normal mammary gland biology and determine how pregnancy associated changes in the mammary gland contribute to development of breast cancers. Though pregnancy is well-known to provide a protective effect against breast cancer risk, all women who give birth experience a transient increase in breast cancer risk following each pregnancy. The magnitude and length of this elevated risk is largely determined by a woman's age at first birth and for women over 30 at the time of first pregnancy the protective effect likely never occurs. Postpartum breast cancers (PPBC), defined as breast cancers diagnosed within 10 years of last childbirth, are more than twice as likely to become metastatic and result in death. This devastating diagnosis affects ~12,000 women annually. In 2006, for the first time, the number of women having children in their 30s was greater than the number under 25. Thus, PPBC cases are rising. We have shown that tumor cells and normal adjacent mammary epithelial cells (MECs) in PPBC patients exhibit high levels of semaphorin 7a (SEMA7A) protein expression, and SEMA7A expressing tumors are more metastatic. Thus, we believe that understanding the mechanisms underlying SEMA7A signaling in the mammary gland will lead to novel insights into aggressive PPBC. Our recent data reveal that SEMA7A+ MECs are evident during lactation, decreased during the reversible phase of postpartum mammary gland involution, and peak at involution day three, suggesting that SEMA7A promotes survival cell survival during postpartum glandular regression. Consistent with our hypothesis, we reveal that mammary luminal progenitor cells are decreased in SEMA7A knockout mice and SEMA7A promotes cell survival in cultured MECs. Interestingly, a portion of our SEMA7A KO dams exhibit evidence of lactation failure, suggestive of precocious involution. Thus, we propose that SEMA7A activates pro-survival signaling in MECs during lactation and involution. In support of this we show that exogenous SEMA7A activates pro-survival kinase AKT in a β1-integrin dependent manner. Additionally, we show that sustained signaling by SEMA7A leads to cellular transformation in vivo and in vitro and that SEMA7A KO mice crossed to MMTV-PyMT mice exhibit longer latency, ~250 days compared to 50-100 in controls. Since we also observe that SEMA7A levels in blood correlate with SEMA7A levels in breast cancer patient tumors, our results suggest that SEMA7A is a driver of tumorigenesis that could be safely monitored in postpartum women. Citation Format: Taylor R. Rutherford, Traci R. Lyons. Semaphorin 7a promotes cellular transformation via activation of pro-survival signaling [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2672.

LIPG endothelial lipase and breast cancer risk by subtypes

Experimental data showed that endothelial lipase (LIPG) is a crucial player in breast cancer. However, very limited data exists on the role of LIPG on the risk of breast cancer in humans. We examined the LIPG-breast cancer association within our population-based case–control study from Galicia, Spain, BREOGAN (BREast Oncology GAlicia Network). Plasma LIPG and/or OxLDL were measured on 114 breast cancer cases and 82 controls from our case–control study, and were included in the present study. The risk of breast cancer increased with increasing levels of LIPG (multivariable OR for the highest category (95% CI) 2.52 (1.11–5.81), P-trend = 0.037). The LIPG-breast cancer association was restricted to Pre-menopausal breast cancer (Multivariable OR for the highest LIPG category (95% CI) 4.76 (0.94–28.77), P-trend = 0.06, and 1.79 (0.61–5.29), P-trend = 0.372, for Pre-menopausal and Post-menopausal breast cancer, respectively). The LIPG-breast cancer association was restricted to Luminal A breast cancers (Multivariable OR for the highest LIPG category (95% CI) 3.70 (1.42–10.16), P-trend = 0.015, and 2.05 (0.63–7.22), P-trend = 0.311, for Luminal A and non-Luminal A breast cancers, respectively). Subset analysis only based on HER2 receptor indicated that the LIPG-breast cancer relationship was restricted to HER2-negative breast cancers (Multivariable OR for the highest LIPG category (95% CI) 4.39 (1.70–12.03), P-trend = 0.012, and 1.10 (0.28–4.32), P-trend = 0.745, for HER2-negative and HER2-positive tumors, respectively). The LIPG-breast cancer association was restricted to women with high total cholesterol levels (Multivariable OR for the highest LIPG category (95% CI) 6.30 (2.13–20.05), P-trend = 0.018, and 0.65 (0.11–3.28), P-trend = 0.786, among women with high and low cholesterol levels, respectively). The LIPG-breast cancer association was also restricted to non-postpartum breast cancer (Multivariable OR for the highest LIPG category (95% CI) 3.83 (1.37–11.39), P-trend = 0.003, and 2.35 (0.16–63.65), P-trend = 0.396, for non-postpartum and postpartum breast cancer, respectively), although we lacked precision. The LIPG-breast cancer association was more pronounced among grades II and III than grade I breast cancers (Multivariable ORs for the highest category of LIPG (95% CI) 2.73 (1.02–7.69), P-trend = 0.057, and 1.90 (0.61–6.21), P-trend = 0.170, for grades II and III, and grade I breast cancers, respectively). No association was detected for OxLDL levels and breast cancer (Multivariable OR for the highest versus the lowest category (95% CI) 1.56 (0.56–4.32), P-trend = 0.457).

The MNK1/2-eIF4E Axis Supports Immune Suppression and Metastasis in Postpartum Breast Cancer.

Breast cancer diagnosed within 10 years following childbirth is defined as postpartum breast cancer (PPBC) and is highly metastatic. Interactions between immune cells and other stromal cells within the involuting mammary gland are fundamental in facilitating an aggressive tumor phenotype. The MNK1/2-eIF4E axis promotes translation of prometastatic mRNAs in tumor cells, but its role in modulating the function of nontumor cells in the PPBC microenvironment has not been explored. Here, we used a combination of in vivo PPBC models and in vitro assays to study the effects of inactivation of the MNK1/2-eIF4E axis on the protumor function of select cells of the tumor microenvironment. PPBC mice deficient for phospho-eIF4E (eIF4ES209A) were protected against lung metastasis and exhibited differences in the tumor and lung immune microenvironment compared with wild-type mice. Moreover, the expression of fibroblast-derived IL33, an alarmin known to induce invasion, was repressed upon MNK1/2-eIF4E axis inhibition. Imaging mass cytometry on PPBC and non-PPBC patient samples indicated that human PPBC contains phospho-eIF4E high-expressing tumor cells and CD8+ T cells displaying markers of an activated dysfunctional phenotype. Finally, inhibition of MNK1/2 combined with anti-PD-1 therapy blocked lung metastasis of PPBC. These findings implicate the involvement of the MNK1/2-eIF4E axis during PPBC metastasis and suggest a promising immunomodulatory route to enhance the efficacy of immunotherapy by blocking phospho-eIF4E. SIGNIFICANCE: This study investigates the MNK1/2-eIF4E signaling axis in tumor and stromal cells in metastatic breast cancer and reveals that MNK1/2 inhibition suppresses metastasis and sensitizes tumors to anti-PD-1 immunotherapy.

Effectiveness of Reverse Pressure Softening of Areola in Women with Postpartum Breast Engorgement

Background and Objectives: Breast engorgement is a frequent problem for lactating mother. It can beextremely painful and may predispose to nipple tenderness, fissures and abscesses. It is associated withtermination of lactation.There are many suggested treatments, these interventions alone did not show anysignificant results.The objective of the research was to study the effectiveness of Reverse Pressure Softeningof Areola in postpartum breast engorgement and to determine whether Reverse Pressure Softening of Areolawith manual expression of milk and proper latching and breastfeeding techniques are effective as comparedto only manual expression of milk and proper latching and breastfeeding techniques.Methods: 80 subjects with postpartum breast engorgement were randomly allocated in two groups. Group-A(40 subjects) underwent interventions such as correction of breastfeeding and latching technique and manualexpression of milk. Whereas in case of group-B (40 subjects) , along with correction of breastfeeding andlatching technique and manual expression of milk, this group was given an additional treatment called as“Reverse Pressure Softening of Areola.” The outcome was assessed in terms of Numeric Pain Rating Scale(NPRS) and Six Point Breast Engorgement Scale (SPBES) at baseline and immediately post intervention.Result and Interpretation: The result of the present study demonstrated significant improvement withexperimental group.Conclusion: Both the interventions in control group and experimental group were found to be individuallyeffective in reducing pain and engorgement of breast among women with postpartum breast engorgement.Further, the reduction observed in pain and engorgement of breast was more among the subjects treated inexperiment than the reduction observed in pain and engorgement of breast in control group.

Antioxidant and antimalarial properties of Sophora exigua Craib. root extract in Plasmodium berghei-infected mice

BackgroundSophora exigua Craib. is commonly used in Thailand to reduce fever and increase postpartum breast milk production in women who have hypogalactia. However, there has been no report on the antioxidant and antimalarial properties of this plant. This study aimed to investigate the antioxidant and antimalarial activities of S. exigua root extract and to evaluate its acute toxicity in mice to confirm its safety.MethodsThe in vitro antioxidant activities were determined using 2,2-diphenyl-1-picrylhydrazyl (DPPH), superoxide radical, and hydroxyl radical scavenging assays. The in vivo antioxidant activities were determined by detecting the malondialdehyde (MDA) content and superoxide dismutase (SOD) activity in the livers of malaria-infected mice. The in vivo antimalarial activity was determined by Peters’ 4-day suppressive test in mice infected with Plasmodium berghei ANKA and orally administered S. exigua root aqueous and ethanolic extracts at different doses (200, 400, and 600 mg/kg body weight). In addition, the acute oral toxicity of the plant extracts was assessed in mice at a dose of 2000 mg/kg body weight.ResultsThe ethanolic extract of S. exigua root exhibited inhibition of DPPH radicals, superoxide anions, and hydroxyl radicals, with half maximal inhibitory concentration (IC50) values of 24.63 ± 1.78, 129.78 ± 0.65, and 30.58 ± 1.19 μg/ml, respectively. Similarly, research on the in vivo antioxidant activity indicated that the ethanolic extract of S. exigua root exerted a stronger effect than the aqueous extract. The aqueous extract at doses of 200, 400, and 600 mg/kg had stronger antimalarial activity than the ethanolic extract. The aqueous extract at 600 mg/kg exhibited 60.46% suppression of parasitemia. Increased levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) and blood urea nitrogen (BUN) were detected in the mice treated with 2000 mg/kg ethanolic extract, which was related to the results of histopathological analysis of liver tissue, showing ballooning degeneration of hepatocytes, diffuse hepatic hemorrhage, and infiltration of inflammatory cells.ConclusionsThis study demonstrated that the ethanolic S. exigua root extract possessed antioxidant properties, and the aqueous extract also had antimalarial activity. Therefore, this plant is an alternative source of new antioxidant and antimalarial agents.

Improving Postpartum Breast Pumping in Mothers of Babies in the NICU

Improving Postpartum Breast Pumping in Mothers of Babies in the NICU

Abstract PD5-10: Mutational burden of the normal breast during age and pregnancy

Abstract Background: The potential for accumulation of somatic mutations in the healthy breast throughout life and pregnancy is poorly understood. In particular, the unique mutational landscape of both epithelial and stromal components of the mammary gland has not been investigated in depth. As cancer risk correlates with both age, age of first-time pregnancy and other factors including pregnancy itself, we wished to study mutational rate over time, using these landmarks. Methods: Here, using whole genome sequencing, we determined how the rate of mutations in both cancer drivers and passenger mutations are affected by both age and pregnancy. We aimed to describe for the first time how the mammary epithelium and stroma differ in their mutational burden. Results: Our analysis of epithelial and stromal laser-capture micro-dissected DNA from 25 normal breast samples of nulliparous and age-matched early- and late-parous women collected from Komen Tissue Bank, University of Indiana, shows that the mammary gland is characterised by known COSMIC signatures SBS1 and SBS5, both of which correlate with age (p&amp;lt;0.05). Using a non-negative matrix factorization approach, we identified a novel signature HB1 for a subset of samples which could not be fitted into the known signature database. Differences between the two cellular compartments were observed mostly in the enrichment pathway of mutated genes, notably a significant enrichment in mutations in the PI3K-Akt signalling pathway in the epithelium. We found that parous stroma is associated with a significant enrichment in mutations in the 3’UTR of genes, suggesting that regulation of the environment in the post-partum breast could preferably occur via these pathways. Alike other normal tissue, the mutational burden of the mammary gland significantly increases with age (P&amp;lt;0.05) and we observed parity-associated patterns of mutational burden, particularly evident in the epithelial compartment. The nulliparous epithelium is characterised by a significant increase of mutations (p&amp;lt;0.05), but mutated clones are maintained at a consistently small size. Conversely, the number of somatic mutations in the parous epithelium is not significantly affected by age, but age is positively correlated with bigger clone sizes (P&amp;lt;0.05) in this group. This trend suggests that possible cancer-associated mutations may have a lower probability of occurring but higher chance of expanding within the parous breast with age, compared to the nulliparous breast. To confirm this, we detected mutations in known driver genes in all the healthy samples, with some occurrence of known individual pathogenic variants.Conclusions: We show the mutational landscape of the healthy breast and highlight differences in the epithelial and stromal cellular compartments. We show how mutated cells, including mutations in driver genes for breast cancer, and genetic alterations change in the contest of pregnancy and age, provide a possible explanation for pregnancy-associated breast cancer risk. Citation Format: Biancastella Cereser, Neha Tabassum, Lisa Del Bel Belluz, Sladjana Zagorac, Angela Yiu, Philip Carter, Cristian Miere, Alicia R Jeffries-Jones, Justin Stebbing. Mutational burden of the normal breast during age and pregnancy [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD5-10.

Abstract PS8-39: Evidence for reproductive control of liver size with implications for risk of liver metastases in postpartum breast cancer patients

Abstract Women diagnosed with breast cancer within 10 years of a completed pregnancy are 2~3x more likely to develop liver metastases than never-pregnant (nulliparous) patients, even after controlling for prognostic variables (Goddard 2017). This finding suggests a unique biology in the postpartum liver, a putative pre-metastatic niche, which makes postpartum patients more susceptible to liver metastases. In rodent models, we previously reported increased liver size, hepatocyte proliferation, and anabolic metabolism during pregnancy and lactation. Within one week post-weaning, the rodent liver returned to its pre-pregnant size via a coordinated cell death and tissue remodeling process we call liver involution (Goddard 2017). We find that this process of involution supports overt liver metastasis using two different mammary tumor cell lines. In women, a liver-breast interaction during pregnancy and weaning, as occurs in rodents, has not been described. To investigate the human liver with pregnancy and weaning, we conducted a prospective, non-interventional clinical trial in healthy pregnant women. 47/77 women completed the pregnancy study visits and 17/47 completed post-wean visits. Participants underwent magnetic resonance imaging (MRI) of their livers, provided blood samples, and completed body metric analyses at each study time point. The majority of women (~70%) had increased liver size and evidence of increased liver function at third trimester compared to first trimester, with liver size returning to pre-pregnancy levels with weaning. In this cohort, the increase in liver size exceeded levels expected if the metabolic demands associated with increased body weight during pregnancy were the primary mediator. Intriguingly, primary bile acid and bile acid synthetic enzyme concentrations correlated with liver size increase during pregnancy. Women whose liver growth did not follow the most often observed pattern of increase with pregnancy and decrease postpartum had unchanged bile acid levels, were more likely to have gestational hypertension, and did not have expected increases in liver glucose production during pregnancy. Combined, this study provides the first description of human liver size increase with pregnancy, and return to pre-pregnant baseline size after weaning, with evidence that women who do not experience these liver changes may be metabolically distinct. Furthermore, these data are consistent with the hypothesis that reproductive alterations to the liver, in particular weaning-induced involution, contributes to the increased risk for liver metastases in women diagnosed with breast cancer postpartum. Reference: Goddard, E. T., Hill, R. C., Nemkov, T., D'Alessandro, A., Hansen, K. C., Maller, O., Mongoue-Tchokote, S., Mori, M., Partridge, A. H., Borges, V. F., &amp; Schedin, P. (2017, Feb). The Rodent Liver Undergoes Weaning-Induced Involution and Supports Breast Cancer Metastasis. Cancer Discov, 7(2), 177-187. https://doi.org/10.1158/2159-8290.CD-16-0822 Citation Format: Alexandra Quackenbush, Erica Goddard, Claire Dorfman, Kimberly Vesco, Jonathan Purnell, Pepper Schedin. Evidence for reproductive control of liver size with implications for risk of liver metastases in postpartum breast cancer patients [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS8-39.

Breast Cancer in the Puerperium. More Questions Than Answers

Breast cancer diagnosed during puerperium and lactation is not fully understandable until today. In general, it is suggested a worse prognosis for postpartum breast cancer compared to breast cancer unrelated to pregnancy or to postmenopausal breast cancer. However, the retrospective nature of some data makes final conclusions less convincing compared to other risk factors related to breast cancer behavior. New research data showed that the screening mammography should be discussed in women aged 40 years and older.

Breast Cancer Cell Detection and Characterization from Breast Milk-Derived Cells.

Radiologic techniques remain the main method for early detection for breast cancer and are critical to achieve a favorable outcome from cancer. However, more sensitive detection methods to complement radiologic techniques are needed to enhance early detection and treatment strategies. Using our recently established culturing method that allows propagation of normal and cancerous breast epithelial cells of luminal origin, flow cytometry characterization, and genomic sequencing, we show that cancer cells can be detected in breast milk. Cells derived from milk from the breast with cancer were enriched for CD49f+/EpCAM-, CD44+/CD24-, and CD271+ cancer stem-like cells (CSC). These CSCs carried mutations within the cytoplasmic retention domain of HDAC6, stop/gain insertion in MORF4L1, and deletion mutations within SWI/SNF complex component SMARCC2. CSCs were sensitive to HDAC6 inhibitors, BET bromodomain inhibitors, and EZH2 inhibitors, as mutations in SWI/SNF complex components are known to increase sensitivity to these drugs. Among cells derived from breast milk of additional ten women not known to have breast cancer, two of them contained cells that were enriched for the CSC phenotype and carried mutations in NF1 or KMT2D, which are frequently mutated in breast cancer. Breast milk-derived cells with NF1 mutations also carried copy-number variations in CDKN2C, PTEN, and REL genes. The approach described here may enable rapid cancer cell characterization including driver mutation detection and therapeutic screening for pregnancy/postpartum breast cancers. Furthermore, this method can be developed as a surveillance or early detection tool for women at high risk for developing breast cancer. SIGNIFICANCE: These findings describe how a simple method for characterization of cancer cells in pregnancy and postpartum breast cancer can be exploited as a surveillance tool for women at risk of developing breast cancer.

Maternal survival of patients with pregnancy-associated cancers in Taiwan - A national population-based study.

Pregnancy‐associated cancer (PAC), defined as cancers diagnosed during pregnancy or the first year after delivery, affects one to two in every 1000 pregnancies. Although PAC is expected to be a growing issue, information about PAC in the Asian population is still scarce. Women with cancer diagnosed at the age of 16–49 years between 2001 and 2015 were selected from the Taiwan Cancer Registry and linked with the National Birth Reporting Database to identify PAC patients. We compared the overall survival of patients with PAC to patients without pregnancy. Among 126,646 female cancer patients of childbearing age, 512 were diagnosed during pregnancy, and 2151 during the first postpartum year. Breast cancer was the most common PAC (N = 755, 28%). Compared with patients without pregnancy in the control group, patients with cancers diagnosed during pregnancy and the first postpartum year generally had more advanced stages (odds ratio 1.35 and 1.36, 95% confidence interval [CI] 1.02–1.77 and 1.18–1.57, respectively). For all cancer types combined and controlled for the stage, age, and year of diagnosis, patients with PAC had similar overall survival with those in the control group, with a hazard ratio (HR) of 1.07 (95% CI 0.80–1.41) for the pregnancy group and HR 1.02 (95% CI 0.88–1.18) for the postpartum group. The diagnosis of breast cancer during the first postpartum year was linked with shorter survival (HR 1.34, 95% CI 1.05–1.72). In contrast, patients with postpartum lymphoma (HR 0.11, 95% CI 0.02–0.79) and cervical cancer (HR 0.40, 95% CI 0.20–0.82) had better prognosis. In general, the diagnosis of cancer during pregnancy or the first postpartum year does not affect the survival of patients with most cancer types. Exceptions include the worse prognosis of postpartum breast cancer and the better outcome of postpartum lymphoma and cervical cancer.

Semaphorin 7a is a biomarker for recurrence in postpartum breast cancer

Breast cancer is a global health threat and cases diagnosed in women during the years after childbirth, or postpartum breast cancers (PPBCs), have high risk for metastasis. In preclinical murine models, semaphorin 7a (SEMA7A) drives the metastatic potential of postpartum mammary tumors. Thus, we hypothesize that SEMA7A may drive metastasis of PPBC in women. We report that SEMA7A protein expression is increased in PPBCs compared to their nulliparous counterparts in our University of Colorado cohort. Additionally, tumors from PPBC patients with involved lymph nodes and lymphovascular invasion were higher on average suggesting a potential role for SEMA7A as a prognostic biomarker. Consistent with this hypothesis we identify a level of SEMA7A expression in tumors that can predict for recurrence. We propose SEMA7A as a potential biomarker and therapeutic target for PPBC patients, who currently lack strong predictors of outcome and unique targeted therapy options.

Contamination, suffering and womanhood: Lay explanations of breast cancer in Central Vietnam.

Breast cancer has become the most frequent cancer among women in Vietnam, claiming over 6000 lives a year. In this article we investigate how laypeople explain the causes of this pressing health issue based on an ethnographic study conducted in the Central region of Vietnam in 2019, including hospital observation, interviews with 33 breast cancer patients and focus groups with 21 laypeople. Our findings show that their knowledge of causation is mediated through historical social contexts of warfare, a rapacious market economy, poverty, and cultural configurations of gender roles. Contamination of the environment and food, use of chemicals, failure to follow postpartum practices, breast ailments, and worry are understood to be immediate determinants of breast cancer. These popular accounts are unlikely to recognize biomedical narratives of breast cancer risk that focus upon individual responsibility and lifestyle factors because they may not reflect the lived realities of women. We emphasise the implications for public awareness campaigns to meaningfully engage with the situated social and cultural specificities of breast cancer.