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Breast cancer in pregnancy

Diagnosis of breast cancer during pregnancy is rare. However, risk of breast cancer increases with age, so more cases are occurring as many women are having children at an older age compared to previous generations. Breasts undergo significant changes when you become pregnant as they develop milk ducts for breast feeding and grow in size. These changes can make it difficult to diagnose breast cancer. Most lumps in the breast found during pregnancy are not cancer, but you should get them checked out by your doctor as soon as possible.

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Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Lin WM, Juan YH, Lin YC, et al.
Awareness of primary spontaneous hemorrhagic angiosarcoma of the breast associated with Kasabach-Merritt syndrome in a pregnant woman by enhanced magnetic resonance imaging: A CARE-compliant case report.
Medicine (Baltimore). 2016; 95(44):e5276 [PubMed] Related Publications
INTRODUCTION: Primary breast angiosarcoma with spontaneous intratumoral bleeding associating with Kasabach-Merritt Syndrome is rarely reported.
CASE FINDINGS/PATIENT CONCERNS: We herein present such a case in a 30-year-old pregnant woman who was initially diagnosed to hemangioma at her early gestation. However, the sudden rapid tumor growth was aware of the attention and intended for receiving the breast enhanced magnetic resonance imaging.
DIAGNOSES AND INTERVENTIONS: The dynamic MRI enhancement showed inhomogenous enhancement at the periphery of the lobulated tumor on both early and delayed scans, otherwise a large hematoma was revealed at the center. Surgical resection was performed after baby delivery by Caeserean section, and histopathologic study confirmed breast angiosarcoma.
CONCLUSION: Despite its rarity, clinicians should recognize the association of breast angiosacroma with Kasabach-Merritt Syndrome with suggestive finding of enhanced MRI in order to decide the surgical approach.

Gentile LF, Gaillard WF, Wallace JA, et al.
A Case of a Giant Borderline Phyllodes Tumor Early in Pregnancy Treated with Mastectomy and Immediate Breast Reconstruction.
Breast J. 2016; 22(6):683-687 [PubMed] Related Publications
Breast tumors in pregnancy are often times diagnosed at advanced stages secondary to difficulty distinguishing between pathologic from normal physiologic changes. Often benign, phyllodes tumors are rare fibroepithelial stromal tumors of the breast, most commonly diagnosed in the 4th and 5th decades of life. However, these tumors may be characterized by malignancy with metastases in 10% of cases. In this paper, we report a novel case of a young woman presenting at 8 weeks gestation with a large borderline phyllodes tumor. An exceedingly rare condition, with only nine previously reported cases, phyllodes tumors in pregnancy frequently display more aggressive characteristics with larger median tumor size, more malignant potential, and more rapid growth rate. Here, we describe our experience safely and effectively treating this rare condition in a young gravid women with mastectomy and immediate breast reconstruction in the second trimester.

Caragacianu DL, Mayer EL, Chun YS, et al.
Immediate breast reconstruction following mastectomy in pregnant women with breast cancer.
J Surg Oncol. 2016; 114(2):140-3 [PubMed] Related Publications
BACKGROUND: Surgical management of breast cancer in pregnancy (BCP) requires balancing benefits of therapy with potential risks to the developing fetus. Minimal data describe outcomes after mastectomy with immediate breast reconstruction (IR) in pregnant patients.
METHODS: Retrospective review was performed of patients who underwent IR after mastectomy within a BCP cohort. Parameters included intra- and post-operative complications, short-term maternal/fetal outcomes, surgery duration, and delayed reconstruction in non-IR cohort.
RESULTS: Of 82 patients with BCP, 29 (35%) had mastectomy during pregnancy: 10 (34%) had IR, 19(66%) did not. All IR utilized tissue expander (TE) placement. Mean gestational age (GA) at IR was 16.2 weeks. Mean surgery duration was 198 min with IR versus 157 min without IR. Those with IR delivered at, or close to, term infants of normal birthweight. No fetal or major obstetrical complications were seen. Post-mastectomy radiation (PMRT) was provided after pregnancy in 2 (20%) patients in the IR cohort and 12 (63%) in the non-IR cohort. All patients in the IR cohort successfully transitioned to permanent implant.
CONCLUSIONS: This report represents one of the largest series describing IR during BCP. IR after mastectomy increased surgery duration, but was not associated with adverse obstetrical or fetal outcomes. IR with TE may preserve reconstructive options when PMRT is indicated. J. Surg. Oncol. 2016;114:140-143. © 2016 Wiley Periodicals, Inc.

Rimawi BH, Green V, Lindsay M
Fetal Implications of Diagnostic Radiation Exposure During Pregnancy: Evidence-based Recommendations.
Clin Obstet Gynecol. 2016; 59(2):412-8 [PubMed] Related Publications
The purpose of this article is to review the fetal and long-term implications of diagnostic radiation exposure during pregnancy. Evidence-based recommendations for radiologic imaging modalities utilizing exposure of diagnostic radiation during pregnancy, including conventional screen-film mammography, digital mammography, tomosynthesis, and contrast-enhanced mammography are described.

Qin W, Dasgupta S, Mukhopadhyay N, Sauter ER
Expression of the Extracellular Matrix Protein Tenascin-C Varies During Lactation.
Breastfeed Med. 2016; 11(2):86-90 [PubMed] Related Publications
BACKGROUND: Women diagnosed with pregnancy-associated breast cancer postpartum have a worse prognosis, stage for stage, than other women with breast cancer. The time of breast involution is tumor promotional. The extracellular matrix protein tenascin-C is upregulated during involution in animal models and promotes breast cancer progression. It interacts with transforming growth factor (TGF)β, which also is involved in breast involution and breast cancer progression. Little is known about the expression of tenascin-C during human breast involution, nor its relationship to TGFβ. The purpose of this study was to investigate the expression of tenascin-C throughout lactation, as well as its relationship to TGFβ1 and TGFβ2.
MATERIAL AND METHODOLOGY: Three milk samples from 25 lactating women (transitional, whole, and wean) were collected, separated into components (cells, fat, and skim), and the skim fraction analyzed for total protein, tenascin-C, TGFβ1, and TGFβ2. Tenascin-C, TGFβ1, and TGFβ2 were detectable in all milk samples.
RESULTS: Highest tenascin-C levels on average were found in whole milk, whereas highest mean TGFβ1 and TGFβ2 levels were in wean milk. Wean samples on average had higher levels of both TGFβ1 (26%) and TGFβ2 (>500%) than matched transitional milk samples. Tenascin-C levels in wean milk were associated with nursing length (p = 0.048). Combining all three milk collection time points, tenascin-C exhibited a weak inverse correlation with TGFβ1 and TGFβ2 (p < 0.1). The inverse correlation at the wean time point was stronger for TGFβ2 than -1 (-0.37 versus -0.25). Tenascin-C, a protein known to promote breast cancer progression, is expressed throughout lactation.
CONCLUSION: The inverse correlation with TGFβ2 in wean milk suggests a possible interaction during breast involution, which should be further investigated.

Andrade JM, Brito LG, Moises EC, et al.
Trastuzumab use during pregnancy: long-term survival after locally advanced breast cancer and long-term infant follow-up.
Anticancer Drugs. 2016; 27(4):369-72 [PubMed] Related Publications
Here, we describe the case of a patient diagnosed with locally advanced breast cancer 8 years ago. Her treatment course was neoadjuvant chemotherapy, followed by mastectomy and then adjuvant radiotherapy and trastuzumab (TTZ). During the use of adjuvant targeted therapy, an incidental pregnancy was diagnosed. Four years later, she developed bone and cerebral metastases, and since then, she has received courses of TTZ, capecitabine, lapatinib, and radiotherapy with intermittent control of the disease. Her 7-year-old son presents a normal physical and long-term neurological developmental curve according to specialized evaluation. This case is unique for several reasons: the patient received the highest dose of TTZ yet described during pregnancy (4400 mg); there has been a long period of disease-free survival after treatment for locally advanced breast cancer and long overall survival despite successive disease progressions during the metastatic phase of the disease (97 months), and there was a monitored pediatric follow-up period (7 years).

Nemescu D, Ursu RG, Nemescu ER, Negura L
Heterogeneous Distribution of Fetal Microchimerism in Local Breast Cancer Environment.
PLoS One. 2016; 11(1):e0147675 [PubMed] Free Access to Full Article Related Publications
Fetal cells enter maternal circulation during pregnancy and persist in the woman's body for decades, achieving a form of physiological microchimerism. These cells were also evidenced in tumors. We investigated the frequency and concentration of fetal microchimerism in the local breast cancer environment. From 19 patients with confirmed breast neoplasia, after breast surgical resection, we collected three fresh specimens from the tumor core, breast tissue at tumor periphery, and adjacent normal breast tissue. The presence of male DNA was analyzed with a quantitative PCR assay for the sex determining region gene (SRY) gene. In the group of women who had given birth to at least one son, we detected fetal microchimerism in 100% of samples from tumors and their periphery and in 64% (9 of 14) of those from normal breast tissue. The tissues from the tumor and its periphery carry a significantly increased number of SRY copies compared to its neighboring common breast tissue (p = 0.005). The median of the normalized SRY-signal was about 77 (range, 3.2-21467) and 14-fold (range, 1.3-2690) greater in the tumor and respectively in the periphery than in the normal breast tissue. In addition, the relative expression of the SRY gene had a median 5.5 times larger in the tumor than in its periphery (range, 1.1-389.4). We found a heterogeneous distribution of fetal microchimerism in breast cancer environment. In women with sons, breast neoplasia harbors male cells at significantly higher levels than in peripheral and normal breast tissue.

Landa A, Kuller J, Rhee E
Perinatal Considerations in Women With Previous Diagnosis of Cancer.
Obstet Gynecol Surv. 2015; 70(12):765-72 [PubMed] Related Publications
As the average age that women have their first child increases and cancer therapies improve survival, obstetricians are more likely to care for pregnant women who have survived cancer. Managing these pregnancies can be challenging, as they may be associated with higher risks of maternal and neonatal morbidity and mortality. Different types of cancer require different types of intervention, including surgery, chemotherapy, radiation, or combinations of these. Prior cancer treatments therefore present different potential complications during pregnancy. Although for most women who survive cancer carrying a pregnancy does not seem to increase mortality rates, there are some associated neonatal morbidities. The most common perinatal complication associated with pregnancy after cancer is prematurity. Women who desire pregnancy after cancer survival should not be discouraged, but appropriate counseling and follow-up should be provided.

Framarino-dei-Malatesta M, Perrone G, Giancotti A, et al.
Epirubicin: a new entry in the list of fetal cardiotoxic drugs? Intrauterine death of one fetus in a twin pregnancy. Case report and review of literature.
BMC Cancer. 2015; 15:951 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Current knowledge indicate that epirubicin administration in late pregnancy is almost devoid of any fetal cardiotoxicity. We report a twin pregnancy complicated by breast cancer in which epirubicin administration was causatively linked to the death of one twin who was small for gestational age (SGA) and in a condition of oligohydramnios and determined the onset of a transient cardiotoxicity of the surviving fetus/newborn.
CASE PRESENTATION: A 38-year-old caucasic woman with a dichorionic twin pregnancy was referred to our center at 20 and 1/7 weeks for a suspected breast cancer, later confirmed by the histopathology report. At 31 and 3/7 weeks, after the second chemotherapy cycle, ultrasound examination evidenced the demise of one twin while cardiac examination revealed a monophasic diastolic ventricular filling, i.e. a diastolic dysfunction of the surviving fetus who was delivered the following day due to the occurrence of grade II placental abruption. The role of epirubicin cardiotoxicity in the death of the first twin was supported by post-mortem cardiac and placental examination and by the absence of structural or genomic abnormalities that may indicate an alternative etiology of fetal demise. The occurrence of epirubicin cardiotoxicity in the surviving newborn was confirmed by the report of high levels of troponin and transient left ventricular septal hypokinesia.
CONCLUSION: Based on our findings we suggest that epirubicin administration in pregnancy should be preceded by the screening of some fetal conditions like SGA and oligohydramnios that may increase its cardiotoxicity and that, during treatment, the diastolic function of the fetal right ventricle should be specifically monitored by a pediatric cardiologist; also, epirubicin and desamethasone for lung maturation should not be closely administered since placental effects of glucocorticoids may increase epirubicin toxicity.

Dabrosin C
An overview of pregnancy and fertility issues in breast cancer patients.
Ann Med. 2015; 47(8):673-8 [PubMed] Related Publications
Breast cancer is one of the most common malignancies of women in the reproductive years. In the Western world there is a trend towards delaying pregnancy to later in life, and in combination with an increased incidence of breast cancer an increased number of women are diagnosed with breast cancer before they have completed their reproductive plans. In addition, breast cancer during pregnancy may affect an increased number of women as the childbearing years are delayed. The survival rate after breast cancer has improved during the last decades, and many young breast cancer survivors will consider a pregnancy subsequent to the completion of adjuvant breast cancer therapy. Traditionally, many women are advised against a pregnancy due to a fear of increased risk of recurrence, especially women with estrogen receptor-positive breast cancer. Due to feasibility issues, evidence from large prospective randomized trials is missing regarding the safety of pregnancy after breast cancer. Today guidelines are based on cohort studies and population-based registry evidence with its limitations. Overall, data suggest that pregnancy after breast cancer therapy is safe, and the current evidence is summarized in this overview.

Ogata H, Kikuchi Y, Natori K, et al.
Liver Metastasis of a Triple-Negative Breast Cancer and Complete Remission for 5 Years After Treatment With Combined Bevacizumab/Paclitaxel/Carboplatin: Case Report and Review of the Literature.
Medicine (Baltimore). 2015; 94(42):e1756 [PubMed] Free Access to Full Article Related Publications
Triple-negative breast cancer (TNBC) is aggressive, with high risk of visceral metastasis and death. A substantial proportion of patients with TNBC is associated with BRCA mutations, implying that these tumors are sensitive to DNA-damaging agents. We report successful treatment of a metastatic TNBC in a woman with a BRCA2 germline mutation using combined bevacizumab/paclitaxel/carboplatin (BPC) therapy. The patient was pregnant and had liver metastases, and a complete clinical response was sustained for approximately 5 years. Mastectomy was performed during the 29th week of pregnancy, and the baby was later delivered by caesarean section. Subsequently, multiple metastases in both liver lobes were detected using computed tomography and magnetic resonance imaging and the patient was treated with a BPC regimen, which led to complete disappearance of metastatic lesions in the liver. No additional treatment was provided, and after 5 years the patient consented to direct sequencing of BRCA2 and a 6781delG mutation was identified. At the most recent (5-year) follow-up, the patient was alive with good quality of life and no evidence of metastases.This finding suggests that BPC therapy might be considered a good therapeutic option for the treatment of metastatic TNBC in a woman with a BRCA2 germline mutation.

Kakoulidis I, Skagias L, Politi E
Pregnancy associated breast cancer (PABC): aspects in diagnosis.
Breast Dis. 2015; 35(3):157-66 [PubMed] Related Publications
Diagnosis of a clinical entity like pregnancy associated breast cancer (PABC) is as demanding and challenging as its rarity. Increasing incidence and controversy that exists in the literature upon prognosis, tumor aggressiveness and underlying mechanisms, highlight the importance of optimizing the diagnostic strategy in women with PABC. Adjustment of standard approach for breast cancer by modifying management methods and options plays key role in decision making. Knowledge of diagnostic modalities and their limitations, in accordance with awareness of physiologic hormone-induced changes of pregnancy and lactation, is the fundamental method of diagnosis in PABC. Thorough triple assessment (history/clinical examination, imaging and cytology/histology) enforces healthcare providers with all essential tools to avoid detrimental delay in diagnosis and to confront with their own hesitation to take action due to limited experience of the disease.

Baulies S, Cusidó M, Tresserra F, et al.
Biological and pathological features in pregnancy-associated breast cancer: a matched case-control study.
Eur J Gynaecol Oncol. 2015; 36(4):420-3 [PubMed] Related Publications
BACKGROUND: The prognosis for breast cancer has been considered to be worsened by the coexistence of pregnancy. However, to date, significant controversy still exists regarding the pathological tumor features and prognosis of patients diagnosed with pregnancy-associated breast cancer (PABC). The aim of the present study was to analyze the different prognostic factors and outcome in PABC subset versus a non-PABC control group matched for age and year of diagnosis.
MATERIALS AND METHODS: A total of 56 PABC cases were diagnosed from 1990 to 2008, for whom 73 non-PABC patients were identified. Pathological characteristics, immunohistochemical fea- tures, and differences in overall and disease-free survival were compared between both groups.
RESULTS: Compared to non-PABC controls, PABC patients presented more advanced disease (31% vs 13%, p = 0.024) and greater lymph node involvement (53% vs 34%, p = 0.034). Pathological and tumor features tended to present poorer prognostic factors in the PABC subset. Survival was poorer in the PABC patients (five-year DFS 68% in PABC vs 86% in non-PABC, p = 0.12). However, analysing survival adjusted for stage and age, the authors did not find significant differences between both groups.
CONCLUSIONS: PABC patients tended to be diagnosed in advanced breast disease and presented tumors with adverse pathological prognostic factors. While the authors found a poorer outcome in PABC group, no significant differences were observed with stage-matched analysis. The present results may suggest that the poorer prognosis observed within PABC women could not be due to pregnancy itself, but with a delay in diagnosis and tumor subtype pathological features.

Leidhin CN, Heeney A, Connolly C, et al.
A Rare Case of BRCA2-Associated Breast Cancer in Pregnancy.
Ir Med J. 2015 Jul-Aug; 108(7):217-8 [PubMed] Related Publications
A 30-year old woman was referred to our department with symptomatic breast cancer at 35 weeks gestation. Genetic testing revealed a pathogenic BRCA2 mutation. Labour was induced at 38 weeks. Mastectomy and axillary clearance were performed with a view to adjuvant chemotherapy, radiation and hormonal therapy. Multidisciplinary involvement is crucial for management of BRCA-associated breast cancer, especially in the context of pregnancy. Bilateral mastectomy may be indicated given the increased risk of ipsilateral and contralateral breast cancers. Tamoxifen may lower contralateral breast cancer risk in those in whom risk-reducing surgery is not performed.

Dietz JR, Partridge AH, Gemignani ML, et al.
Breast Cancer Management Updates: Young and Older, Pregnant, or Male.
Ann Surg Oncol. 2015; 22(10):3219-24 [PubMed] Related Publications
Every year, more and more patients fall into rare or extreme categories of breast cancer-young, elderly, pregnant, or male. Contributing factors may be improved risk assessment and screening techniques (especially of dense breast tissue), delayed childbearing, and the aging population. These patients can challenge usual medical decision making because of their unique situation. There might be a concern for the fetus, worry about future fertility, a question of local control in a man, or concern for overdiagnosis or overtreatment in an older patient. Because these populations are seldom included in the large breast cancer trials from which standard treatment recommendations are made, an update on management for young, elderly, pregnant, and male breast cancer patients may be helpful.

Loibl S, Schmidt A, Gentilini O, et al.
Breast Cancer Diagnosed During Pregnancy: Adapting Recent Advances in Breast Cancer Care for Pregnant Patients.
JAMA Oncol. 2015; 1(8):1145-53 [PubMed] Related Publications
Breast cancer during pregnancy (BCP), although rare, is becoming more common and treatment should be as similar as possible to that for nonpregnant young patients with breast cancer. A group of specialists convened to review current guidelines and provide guidance on how recent advances in breast cancer diagnosis and treatment can be adapted for pregnant patients. The majority of patients with BCP will be considered for treatment during the pregnancy. Premature delivery should be avoided whenever possible. Most treatments, including sentinel lymph node biopsy, systemic therapy with taxanes, platinum agents, or dose-dense treatment can be safely given during pregnancy, after careful risk/benefit assessment for mother and child. Chemotherapy is contraindicated during the first trimester because of a higher risk of fetal malformations but is feasible in the second and third trimesters. Other treatments such as radiation therapy or anti-human epidermal growth receptor 2 treatment are in general not indicated during pregnancy but might be considered in some instances. Patient data should be collected in a systematic way whenever possible.

Lambertini M, Kamal NS, Peccatori FA, et al.
Exploring the safety of chemotherapy for treating breast cancer during pregnancy.
Expert Opin Drug Saf. 2015; 14(9):1395-408 [PubMed] Related Publications
INTRODUCTION: The diagnosis of breast cancer during pregnancy (BCP) represents a unique challenge to the patient, her family and the treating physician. The proper management of this critical clinical situation is crucial, and requires a multidisciplinary approach. A proper understanding of the safety of chemotherapy during pregnancy is a vital step to avoid detrimental consequences on the mother and the fetus.
AREAS COVERED: The aim of this article is to review the available evidence on the safety of chemotherapy administration in managing BCP.
EXPERT OPINION: The rule of thumb of chemotherapy - avoiding first trimester exposure and starting therapy in the second trimester - can be considered applicable for classic agents that are used in managing pregnant breast cancer patients. Anthracycline-based regimens are considered the standard of care in managing BCP. Recently, a growing amount of data suggests the safety of taxanes during pregnancy. Pregnancy in cancer patients should be considered as "high risk": once the systemic treatment is initiated, regular fetal monitoring is highly recommended. Emerging data are available on the relative long-term safety secondary to anthracycline exposure during pregnancy. A continued monitoring of the health of individuals with prenatal exposure to chemotherapy into adulthood is recommended for the possible occurrence of long-term side effects.

Huang Y, Zhang H, Zhou Q, et al.
Giant tubular adenoma of the accessory breast in the anterior chest wall occurred in a pregnant woman.
Diagn Pathol. 2015; 10:60 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Tubular adenoma of the breast is a rare benign epithelial tumor and only a few literatures have been reported; so far, no cases of tubular adenoma occurred in the accessory breast have been reported in the English literature. Clinical presentation and management of our patient are discussed along with a review of the literature on accessory mammary and tubular adenoma.
CASE PRESENTATION: We present a case of 26-year-old woman (gravid 4, para 1) at 37 weeks of pregnancy with rapid enlargement in left anterior chest wall during pregnancy. Physical examination showed the left accessory breast was obviously bigger than the right one that only had a light areola around a small nipple. An elastic, mobile well-circumscribed mass measuring approximately 15 cm × 15 cm was palpated. Moreover, it was edematous and congestive with an increase in local temperature. The breast ultrasound further demonstrated the mass was a relatively homogeneous solid with short stripe blood flow signal. A single live fetus of 37 weeks gestation was observed by abdominal ultrasound scan. After a 2850 g male neonate was delivered, the right accessory breast and the mass in left accessory breast were removed. The resected specimen appeared as a solid white elastic mass with a smooth surface and the cut surface was red-grayish. Microscopically, the lesion consisted of tightly packed homogenous glandular structures which are supported by a single layer of myoepithelial cells with sparse intervening stroma.
CONCLUSIONS: We describe a very rare case of giant tubular adenoma arising within an accessory breast in the anterior chest wall in a late pregnancy woman. The high concentrations of estrogen, progesterone and prolactin might account for the significant tumor enlargement during pregnancy. To our knowledge, this is the first case of giant tubular adenoma occurred within the accessory breast in the anterior chest wall.
VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/6210811191552106 .

Johansson AL, Andersson TM, Hsieh CC, et al.
Family history and risk of pregnancy-associated breast cancer (PABC).
Breast Cancer Res Treat. 2015; 151(1):209-17 [PubMed] Related Publications
The risk of breast cancer is at least two-fold increased in young women with a family history of breast cancer. Pregnancy has a dual effect on breast cancer risk; a short-term increase followed by a long-term protection. We investigated if the risk of breast cancer during and within 10 years following pregnancy is affected by a family history of breast cancer. We followed a cohort of women aged 15-44 years between 1963 and 2009 identified in Swedish population-based registers. Family history was defined as having a mother or sister with breast cancer. We estimated incidence rate ratios of breast cancer during pregnancy and time intervals up to 10 years post-delivery, with a focus on pregnancy-associated breast cancer (PABC), defined as breast cancer during pregnancy or within 2 years post-delivery. In 3,452,506 women, there were 15,548 cases of breast cancer (1208 were PABC). Compared to nulliparous women, the risk of breast cancer was decreased during pregnancy, similar during first year and increased during second year post-delivery. The pattern was similar in women with or without family history of breast cancer. A peak in risk was observed 5-6 years following the first birth regardless of family history. After a second birth, this peak was only present in women with a family history. Our results indicate that women with a family history of breast cancer do not have a different breast cancer risk during and within 10 years following pregnancy compared to women without a family history.

Azim HA, Vingiani A, Peccatori F, et al.
Tumour infiltrating lymphocytes (TILs) in breast cancer during pregnancy.
Breast. 2015; 24(3):290-3 [PubMed] Related Publications
BACKGROUND: Tumour infiltrating lymphocytes (TILs) is one of the most exciting breast cancer biomarkers, yet no data is available on its prevalence in tumours diagnosed during pregnancy.
METHODS: We evaluated the prevalence of TILs (stromal and intratumoural) in pregnant and non-pregnant young breast cancer patients.
RESULTS: 11/116 (9.6%) of the non-pregnant and 2/86 (2.3%) pregnant patients had TILs ≥ 50% (p < 0.001) with highest prevalence observed in triple negative tumours (p = 0.01).
CONCLUSIONS: This is the first report on TILs in tumours diagnosed during pregnancy. The low prevalence could reflect the state of low host immunity associated with pregnancy.

Mizejewski GJ
Cancer during pregnancy: what is the role of maternal serum and placental biomarkers? A review and commentary.
Tumori. 2014 Nov-Dec; 100(6):581-9 [PubMed] Related Publications
Cancer during pregnancy, referred to as gestational cancer (GC), is infrequent but can occur in 1.0% of pregnant women. Hepatocellular carcinoma (HCC) is often lethal and is the fifth most common cancer worldwide, while breast adenocarcinoma (breast cancer) is the most common cancer seen during pregnancy. Liver and breast carcinomas are two examples of cancer types that present challenges to the obstetrician due to late and/or delayed diagnosis during pregnancy. Delays in diagnosis limit choices available to physicians regarding surgery, radiation, and chemotherapy. In view of such clinical situations, a role for maternal serum and placental biomarker (MSPB) screening results contributing to cancer diagnosis should be recognized; overlooking such data in GC could result from a lack of knowledge and understanding of MSPB biology, chemistry, and physiology. In this report, obstetricians and perinatologists seeking a diagnosis are urged to take advantage of available results from MSPB screening programs obtained from first- and second-trimester patient data. Using liver and breast cancer as examples, the present review and commentary seeks to demonstrate that MSPB levels, profiles, patterns, and cellular responses could provide foundational data in planning invasive or noninvasive methods and procedures (biopsy, imaging, scans, surgery) to attain a diagnosis as soon as possible in pregnancy. Finally, MSPB epidemiological and cancer risk studies could aid in providing baseline information for decisions regarding GC diagnosis from knowledge of their proposed roles in reducing lifetime risk of malignancies such as breast cancer.

Pagani O, Ruggeri M, Manunta S, et al.
Pregnancy after breast cancer: Are young patients willing to participate in clinical studies?
Breast. 2015; 24(3):201-7 [PubMed] Related Publications
Young patients with breast cancer (BC) are often concerned about treatment-induced infertility and express maternity desire. Conception after BC does not seem to affect outcome, but information in estrogen-receptor positive (ER+) disease is not definitive. From September 2012-March 2013, 212 evaluable patients with ER+ early BC, <37 years at diagnosis, from 5 regions (Europe/US/Canada/Middle-East/Australia) answered a survey about fertility concerns, maternity desire and interest in a study of endocrine therapy (ET) interruption to allow pregnancy. Overall, 37% of respondents were interested in the study; younger patients (≤30 years) reported higher interest (57%). Motivation in younger patients treated >30 months was higher (83%) than in older women (14%), interest was independent of age in patients treated for ≤30 months. A prospective study in this patient population seems relevant and feasible. The International-Breast-Cancer-Study-Group (IBCSG), within the Breast-International-Group (BIG) - North-American-Breast-Cancer-Groups (NABCG) collaboration, is launching a study (POSITIVE) addressing ET interruption to allow pregnancy.

Epstein Shochet G, Drucker L, Pasmanik-Chor M, et al.
First trimester human placental factors induce breast cancer cell autophagy.
Breast Cancer Res Treat. 2015; 149(3):645-54 [PubMed] Related Publications
Placental factors, progesterone included, facilitate breast cancer cell line (BCCL) motility and thus may contribute to the advanced breast cancer found during pregnancy. Cancer and placental implantations are similar; the last is accompanied by extravillous trophoblast cell invasion and autophagy which are interlinked. We aimed to analyze the effect of first trimester human placenta on BCCL autophagy. BCCLs (MCF-7/T47D) were cultured with placental explants (60 h) or placental supernatants (24 h). Following cultures, BCCLs were sorted out for RNA/protein extraction. RNA served for microarray/qPCR (BNIP3) and protein for Western blot (HIF1α, LC3BII) analyses. Inhibitors were added to the placenta-MCF-7 coculture or placental supernatants (autophagy inhibitor-3MA, progesterone receptor (PR) inhibitor-RU486, and HIF1α inhibitor-Vitexin) in order to evaluate their effects on BCCL motility and LC3BII/HIF1α expression. LC3BII (an autophagy marker) expression was elevated in BCCLs following placental explant coculture and exposure to placental supernatants. The autophagy inhibitor (3MA) repressed the placenta-induced MCF-7/T47D migration, establishing a connection between BCCL autophagy and migration. Microarray analysis of MCF-7 following placenta-MCF-7 coculture showed that "HIF1α pathway," a known autophagy facilitator, was significantly manipulated. Indeed, placental factors elevated HIF1α and its target BNIP3 in the BCCLs, verifying array results. Lastly, PR inhibitor reduced HIF1α expression and both PR and HIF1α inhibitors reduced MCF-7 LC3BII expression and motility, suggesting involvement of the PR-HIF1α axis in the autophagy process. Placental factors induced BCCL autophagy that is interlinked to their motility. This suggests that autophagy-related molecules may serve as targets for therapy in pregnancy-associated breast cancer.

Adeniji-Sofoluwe AT, Obajimi GO, Obajimi MO
Pregnancy related breast diseases in a developing African country: Initial Sonographic Evaluation.
Pan Afr Med J. 2015; 20:239 [PubMed] Free Access to Full Article Related Publications
Benign diseases are more common than malignant diseases in pregnant and lactating women. Fibroadenomas are the most commonly identified benign breast tumour in pregnant and lactating women. Pregnancy related breast cancer is defined as breast cancer that occurs during pregnancy or within 1 year of delivery. Its incidence is estimated at 1 in 3000 to 1 in 10 000 pregnancies. Several reproductive factors like age at menarche, age at menopause, age at full-term pregnancy, parity, age at any birth and spacing of pregnancies, breast feeding, characteristics of the menstrual cycle, infertility, spontaneous and induced abortions, characteristics of the menstrual cycle and infertility are some of the factors that have been incriminated as risk factors for breast cancer. We sought to describe the predominant breast pattern, sonographic array of pregnancy related breast diseases in women referred to the breast imaging unit in the department of Radiology at the University College Hospital, Ibadan south west Nigeria. Socio-demographic characteristics in these women were also evaluated. Archived images were reviewed and documented and data was analysed with SPSS version 17 and presented with descriptives. In this descriptive study, we retrospectively retrieved the sonomammographic records of 21 women (pregnant or lactating) referred to and imaged in the department of radiology, University college hospital Ibadan, between 2006 and 2013. Diagnostic breast sonograms performed by MO and ATS; Consultant radiologists with 7-10 years' experience utilized a 7-10 MHz transducer of the General electric GE Logiq P5 machine for the scans. Twenty-one women with ages between 22-42 years (Mean 31.4 ± 5.4 SD) pregnant or lactating were referred to the radiology department for sonomammographic evaluation. Majority of the women were in the 3rd decade. Referral was mainly (11) by family Physicians from the general outpatient clinic, 5 were self-referred, 2 from radiotherapy department, 2 from obstetrics and gynaecology department and 1 from the surgical outpatient clinic. Nineteen (89.5%) were lactating and breastfeeding while 2 (10.5%) were pregnant. Nipple discharge (89.5%) was the predominant presenting complaint in the study. They were all married with the majority attaining menarche at age 14.6 ± 2.1 SD years. Most of the women were multi-parous 17(89.5%) and possessed higher level of Education 17 (81.0%). Twenty (96.0%) women had no previous breast disease while only 1 (4.0%) woman had a positive family history of breast cancer. They weighed between 44-102 kg (mean 69.84 kg ± 15.33 SD). Their mean height was 159.8 cm. Waist hip ratio was between 0.69-0.93 (Mean 0.83). The heterogeneous fibroglandular pattern was predominant in 15 (71.4%) women. Final BIRADS assessment of 2 was most frequent (11/21) 52.4% while 19.0% were assigned to BIRADS categories 0 and 1 (4/21). Histological diagnosis of Invasive ductal carcinoma was made in the 3 women with final BIRADS of 5 breast diseases found in most pregnant and lactating women were benign. It is important to note that malignant breast lesions can also occur in this group of women who may assume that the changes noted in their breast are due to lactation.

Murthy RK, Theriault RL, Barnett CM, et al.
Outcomes of children exposed in utero to chemotherapy for breast cancer.
Breast Cancer Res. 2014; 16(6):500 [PubMed] Free Access to Full Article Related Publications
INTRODUCTION: The incidence of breast cancer diagnosed during pregnancy is expected to increase as more women delay childbearing in the United States. Treatment of cancer in pregnant women requires prudent judgment to balance the benefit to the cancer patient and the risks to the fetus. Prospective data on the outcomes of children exposed to chemotherapy in utero are limited for the breast cancer population.
METHODS: Between 1992 and 2010, 81 pregnant patients with breast cancer were treated in a single-arm, institutional review board-approved study with 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC) in the adjuvant or neoadjuvant setting. Labor and delivery records were reviewed for each patient and neonate. In addition, the parents or guardians were surveyed regarding the health outcomes of the children exposed to chemotherapy in utero.
RESULTS: In total, 78% of the women (or next of kin) answered a follow-up survey. At a median age of 7 years, most of the children exposed to chemotherapy in utero were growing normally without any significant exposure-related toxicity or health problems. Three children were born with congenital abnormalities: one each with Down syndrome, ureteral reflux or clubfoot. The rate of congenital abnormalities in the cohort was similar to the national average of 3%.
CONCLUSIONS: During the second and third trimesters, pregnant women with breast cancer can be treated with FAC safely without concerns for serious complications or short-term health concerns for their offspring who are exposed to chemotherapy in utero. Continued long-term follow-up of the children in this cohort is required.
TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00510367. Other Study ID numbers: ID01-193, NCI-2012-01578. Registration date: 31 July 2007.

Kasum M, Beketić-Orešković L, Orešković S
Subsequent pregnancy and prognosis in breast cancer survivors.
Acta Clin Croat. 2014; 53(3):334-41 [PubMed] Related Publications
An increase in the incidence of breast cancer in women aged < 40 years in conjunction with a pronounced shift towards later childbearing has been reported in recent years. Because survival from breast cancer in women of childbearing age has significantly improved, they are often concerned whether subsequent pregnancy will alter their risk of disease recurrence. In the modern era, the prognosis of pregnancy-associated breast cancer is comparable to non-pregnancy-associated breast cancer and women can bear children after breast cancer treatment without compromising their survival. Therefore, they should not be discouraged from becoming pregnant, and currently the usual waiting time of at least 2 years after the diagnosis of breast cancer is recommended. However, a small, nonsignificant adverse effect of pregnancy on breast carcinoma prognosis among women who conceive within 12 months of breast cancer diagnosis and a higher risk of relapse in women younger than 35 up to 5 years of the diagnosis may be found. Fortunately, for women with localized disease, earlier conception up to six months after completing their treatment seems unlikely to reduce their survival. Ongoing and future prospective studies evaluating the risks associated with pregnancy in young breast cancer survivors are required.

Strasser-Weippl K, Ramchandani R, Fan L, et al.
Pregnancy-associated breast cancer in women from Shanghai: risk and prognosis.
Breast Cancer Res Treat. 2015; 149(1):255-61 [PubMed] Related Publications
Breast cancer (BC) has been associated with pregnancy if diagnosed within 5-10 years after delivery (pregnancy-associated BC, PABC). PABC carries a poor prognosis compared to sporadic BC in Western populations. Data are limited regarding PABC in Asian populations, where longer periods of breastfeeding, higher birth rates and a lower median age of BC at diagnosis have been noted, all of which are known to influence prognosis. We used two datasets of women treated for early BC in Shanghai 1990-2012 (n = 10,161 and n = 7,411). For the analysis of BC risk after pregnancy we compared the distribution of pregnancy in our dataset to that in Shanghai using age-specific fertility rates. For disease-free survival (DFS) evaluation, we restricted our data to women ≤45 years. Women <30 years had a significantly elevated BC risk within 5 years of completing a pregnancy compared to women who had not been pregnant in the previous 5 years. In women aged 20-24 the relative risk (RR) was 3.33 (P = 0.012), and for women aged 25-29 the RR was 1.76 (P = 0.0074). For women >30, the RR was decreased. Patients with PABC had a higher risk of recurrence or death (hazard ratio (HR) for DFS 1.72, P = 0.019) compared to women with non-PABC by univariable analysis. Age was eliminated from the multivariable model by backward selection, resulting in tumor stage (3 versus 1, HR 3.08, P < .001) and recent pregnancy (HR 1.62, P < 0.05) as significant independent prognosticators. Having had a full-term pregnancy in the previous 5 years was associated with a 62 % increased risk of recurrence. We show that recent full-term pregnancy significantly elevates BC risk in women <30 in Shanghai, and that women diagnosed with PABC have a particularly adverse prognosis. Health care providers and women in Asian populations should be made aware of these results.

Rossi RE, Naik K, Navalkissoor S, et al.
Case report of multimodality treatment for metastatic parathyroid hormone-related peptide-secreting pancreatic neuroendocrine tumour.
Tumori. 2014 Jul-Aug; 100(4):153e-6e [PubMed] Related Publications
AIMS AND BACKGROUND: Hypercalcaemia due to metastatic parathyroid hormone-related peptide-secreting pancreatic neuroendocrine tumour is challenging to manage and requires a multimodality approach.
METHODS: We present a case of a woman undergoing liver transplantation for metastatic parathyroid hormone-related peptide-secreting pancreatic neuroendocrine tumour.
RESULTS: A young woman with a history of parathyroid hormone-related peptide-secreting pancreatic neuroendocrine tumour (Ki-67 5%) removed in 1998 developed bilobar liver metastases in 2004 and underwent repeated transarterial embolisations of liver tumour and therapy with somatostatin analogue. In view of symptomatic hypercalcaemia refractory to medical therapy, she underwent liver transplantation in 2006. In 2012, follow-up imaging showed a 3-cm hypervascular lesion in the posterior wall of the stomach, which was confirmed on endoscopic ultrasound and on gallium-68-octreotate positron emission tomography scan. A gastric wall resection was performed in February 2013, and biopsies showed a neuroendocrine tumour of intermediate grade (Ki-67 15%). In June 2013, a restaging imaging showed a 2.4 cm lesion in the left breast, which was reported as a primary breast cancer on biopsies, and a 14-mm tissue lesion anterior to the gastric antrum. The patient underwent surgical excision of the breast cancer followed by hormone treatment and radiotherapy. She had surgical removal of the gastric recurrence with adjuvant chemotherapy postoperatively.
CONCLUSIONS: Hypercalcaemia related to parathyroid hormone-related peptide-secreting neuroendocrine tumour can be life-threatening, and liver transplantation may be a viable option in case of liver only diffuse neuroendocrine metastases refractory to other therapies. The risk of tumour recurrence remains a significant clinical problem after liver transplantation, and only a few patients might be considered tumour-free 5 years after liver transplantation.

Ross M, Hadzikadic Gusic L, Dabbs DJ, et al.
Simultaneous breast and axillary recurrence in a patient with a history of breast cancer and ipsilateral upper extremity melanoma: challenges in diagnosis and management.
Tumori. 2014 Jul-Aug; 100(4):136e-9e [PubMed] Related Publications
BACKGROUND: Nodal patterns of spread for breast cancer and melanoma have been extensively studied in the literature. The phenomenon of upper extremity melanoma and ipsilateral breast cancer has been previously reported. We describe a rare case of a simultaneous locoregional recurrence of both malignancies.
CASE REPORT: A patient with a previous diagnosis of stage 1A melanoma of the left upper extremity at age 29 developed left breast invasive ductal carcinoma 1 year later. The patient underwent a wide local excision with negative margins for the melanoma and a partial mastectomy with axillary dissection followed by chemotherapy and radiation therapy for her breast cancer. Five years later she was diagnosed with a dual recurrence while 36 weeks pregnant.
CONCLUSIONS: Regular follow-up according to the NCCN guidelines is critical in diagnosing a recurrence of malignancy. Pathologic analysis is paramount in dictating management strategies in rare cases of dual recurrence.

Luo M, Zeng J, Li F, et al.
Safety of pregnancy after surgical treatment for breast cancer: a meta-analysis.
Int J Gynecol Cancer. 2014; 24(8):1366-72 [PubMed] Related Publications
PURPOSE: Because of the rising trend of delayed pregnancies, more and more women remain nulliparous at the diagnosis of breast cancer, and approximately 71% of them desire to conceive after breast cancer treatment. Advances in breast cancer screening have made early diagnosis of breast cancer possible, and many patients have the opportunity to be treated by surgery. In this study, we conducted a meta-analysis to evaluate the effect of pregnancy on patient survival and prognosis after surgical treatment for breast cancer.
METHODS: An electronic search was performed in MEDLINE (PubMed), EMBASE, and Web of Science to identify potentially eligible studies published before August 2013. Both fixed-effect and random-effect models were used to calculate the pooled relative risk (PRR). The Q test and I(2) statistics were used to assess the heterogeneity among the studies.
RESULTS: A total of 5 studies were included in our meta-analysis. Five hundred fifty-four patients who become pregnant after surgical treatment for breast cancer were compared with a control group of 2354 patients for overall survival (OS). Our analysis demonstrated that pregnancy after surgical treatment for breast cancer had a significant beneficial effect on OS (PRR, 0.78; 95% confidence interval, 0.64-0.95). The disease-free survival outcome also favored patients in the pregnancy group (PRR, 0.87; 95% confidence interval, 0.71-1.08).
CONCLUSIONS: This meta-analysis indicates that pregnancy after surgical treatment does not increase the risk of breast cancer recurrence and may actually improve OS.

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