{"product_id":"breast-cancer-during-pregnancy-a-comprehensive-guide-to-diagnosis-treatment-and-safety-for-mother-and-baby","title":"Breast Cancer During Pregnancy: A Comprehensive Guide to Diagnosis, Treatment, and Safety for Mother and Baby","description":"\u003cp\u003eBreast cancer is the most common cancer diagnosed during pregnancy, affecting roughly 1 in 3,000 to 1 in 10,000 pregnant women — about 2,000 to 4,000 women in Europe each year. This comprehensive review explains that pregnant patients should receive the same state-of-the-art cancer treatment as non-pregnant patients whenever possible, with the pregnancy maintained as long as possible. Breast cancer during pregnancy is more often triple-negative (38.9% vs 26.9%). Breast cancer during pregnancy is less often hormone-receptor positive than in age-matched non-pregnant patients. Diagnosis is frequently delayed because normal pregnancy changes mask the signs. Surgery is safe in every trimester. Radiotherapy is possible in the first half of pregnancy. Chemotherapy can be given safely from 12 weeks of gestation. But endocrine (hormone-blocking) therapy and HER2-targeted therapy are contraindicated throughout pregnancy.\u003c\/p\u003e\n\n\u003ch1\u003eBreast cancer during pregnancy- epidemiology, phenotypes, presentation during pregnancy and therapeutic modalities\u003c\/h1\u003e\n\n\u003ch2\u003eTable of Contents\u003c\/h2\u003e\n\u003cul\u003e\n\u003cli\u003e\u003ca href=\"#ddn-key-points\"\u003eKey Points\u003c\/a\u003e\u003c\/li\u003e\n\n  \u003cli\u003e\u003ca href=\"#background\"\u003eWhy This Research Matters\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#epidemiology\"\u003eHow Common Is Breast Cancer During Pregnancy?\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#presentation\"\u003eHow Breast Cancer Shows Up During Pregnancy\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#diagnosis\"\u003eDiagnosing Breast Cancer During Pregnancy\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#radiation\"\u003eUnderstanding Radiation Risk to the Fetus\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#phenotypes\"\u003eTumor Types and Biology\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#treatment\"\u003eTreatment Principles: The Big Picture\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#surgery\"\u003eSurgery During Pregnancy\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#safety\"\u003eSentinel Lymph Node Staging and Medication Safety\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#implications\"\u003eWhat This Means for Patients\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#limitations\"\u003eLimitations of the Evidence\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#recommendations\"\u003ePractical Recommendations\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#ddn-faq\"\u003eFrequently Asked Questions\u003c\/a\u003e\u003c\/li\u003e\n\u003cli\u003e\u003ca href=\"#source\"\u003eSource Information\u003c\/a\u003e\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003c!-- ddn:keypoints:start --\u003e\n\u003ch2 id=\"ddn-key-points\"\u003eKey Points\u003c\/h2\u003e\n\u003cul\u003e\n\u003cli\u003eBreast cancer is the most common cancer during pregnancy, affecting about 1 in 3,000 to 1 in 10,000 pregnant women, or 2,000 to 4,000 women in Europe yearly.\u003c\/li\u003e\n\u003cli\u003eSurgery is safe in every trimester, radiotherapy is possible in the first half of pregnancy, and chemotherapy can be given safely from 12 weeks of gestation.\u003c\/li\u003e\n\u003cli\u003eEndocrine (hormone-blocking) therapy and HER2-targeted therapy are contraindicated throughout pregnancy and must wait until after delivery.\u003c\/li\u003e\n\u003cli\u003eAny suspicious breast lump or nipple discharge lasting 2 weeks or more during pregnancy should be investigated, even though about 80% of such lesions are benign.\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003c!-- ddn:keypoints:end --\u003e\n\n\n\u003ch2 id=\"background\"\u003eWhy This Research Matters\u003c\/h2\u003e\n\u003cp\u003eCancer during pregnancy is rare. About 1 in 1,000 pregnancies is complicated by cancer in the mother, and breast cancer is the most frequent of these cancers. The authors of this review point out that the number of cases is likely to rise. Two trends drive this increase. Women are delaying pregnancy to older ages. Wider use of genome-wide non-invasive prenatal testing is turning up incidental maternal cancers during pregnancy. This blood test on the mother screens for fetal chromosomal abnormalities.\u003c\/p\u003e\n\n\u003cp\u003eTreating cancer during pregnancy is a balancing act. Doctors must protect the mother's life while protecting the developing fetus. The authors stress that a dedicated multidisciplinary team — specialists in many fields working together — is essential. In 2012, the Netherlands founded a multidisciplinary Advisory Board Cancer in Pregnancy. This virtual tumor board gives clinicians fast access to individually tailored advice on diagnostic and treatment dilemmas. Its members include cancer surgeons, gynecological oncologists, experts in obstetrical medicine, fertility experts, radiation oncologists, medical oncologists, hematologists, pediatric oncologists and pediatricians, imaging specialists, a clinical pharmacologist, and an ethicist.\u003c\/p\u003e\n\n\u003cp\u003eThe core principle is simple to state and hard to execute. Women should receive state-of-the-art cancer treatment without delay whenever possible. The pregnancy should be maintained as long as possible. Treatment strategy should be defined by a multidisciplinary team that carefully weighs the selection, sequence, and timing of each treatment modality. Starting cancer treatment during pregnancy often lowers the risks of early delivery and prematurity.\u003c\/p\u003e\n\n\u003ch2 id=\"epidemiology\"\u003eHow Common Is Breast Cancer During Pregnancy?\u003c\/h2\u003e\n\u003cp\u003eBreast cancer is the most commonly diagnosed cancer during pregnancy. This simply reflects how common cancer is in women of reproductive age — about 10% of all breast cancer patients are under 40 years old.\u003c\/p\u003e\n\n\u003cp\u003eIn adolescents and young adults (AYA, defined as ages 15 to 39), breast cancer is the most common cancer diagnosis. The age-adjusted rate is 22.9 new cases per 100,000 female AYAs, and the age-adjusted death rate is 2.2 per 100,000 female AYAs.\u003c\/p\u003e\n\n\u003cp\u003eThe terminology in this field has been inconsistent. The terms \"pregnancy-associated breast cancer\" (PABC) and \"breast cancer during pregnancy\" (PrBC) have been used loosely. PABC often lumps together breast cancer diagnosed during pregnancy and breast cancer diagnosed within 6 months to 1 year after delivery. More recently, experts advocate separating breast cancer diagnosed during pregnancy (PrBC) from breast cancer that occurs during the postpartum period (PPBC), which may extend to 5 to 10 years after birth.\u003c\/p\u003e\n\n\u003cp\u003eThe numbers break down as follows:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003e\n\u003cstrong\u003e0.2% to 2.6%\u003c\/strong\u003e of all breast cancers occur during pregnancy.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003e35% to 55%\u003c\/strong\u003e of all breast cancer cases in women under 45 are estimated to occur within 5 to 10 years after pregnancy.\u003c\/li\u003e\n  \u003cli\u003ePrBC is found in \u003cstrong\u003e1 in 3,000 to 1 in 10,000\u003c\/strong\u003e women, which corresponds to roughly \u003cstrong\u003e2,000 to 4,000\u003c\/strong\u003e pregnant women in Europe each year.\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003eNo specific risk factors for PrBC have been identified. The same genetic and environmental risk factors seen in age-adjusted breast cancer in the general population apply. However, women with a BRCA1 germline mutation (an inherited mutation in a gene that normally repairs DNA) appear to have an increased risk of developing PrBC. One study of 20 women with pregnancy-associated breast cancer used a 94-cancer-gene panel and found that 7 of the women carried pathogenic mutations in BRCA1 or CHEK2. Because of their young age at diagnosis and the clinical consequences for relatives, women with PrBC should be referred for genetic counselling.\u003c\/p\u003e\n\n\u003ch3\u003eWhat a Large International Cohort Found\u003c\/h3\u003e\n\u003cp\u003eThe International Network on Cancer, Infertility and Pregnancy (INCIP) studied 1,170 patients over a 20-year period. Researchers found that 67% of patients received cancer treatment during pregnancy, and that the likelihood of receiving treatment during pregnancy increased over time. This increase was mainly related to greater use of chemotherapy.\u003c\/p\u003e\n\n\u003cp\u003eAmong 1,089 singleton pregnancies, 955 (88%) resulted in a live birth, and 48% of those babies were delivered preterm. Over time, there were more live births and fewer iatrogenic preterm deliveries (preterm deliveries deliberately induced for medical reasons). However, exposure to antenatal chemotherapy was associated with more fetal complications. Antenatal chemotherapy is chemotherapy given before birth. Specifically, there were more neonates who were small for gestational age. There were also more admissions to the neonatal intensive care unit (NICU).\u003c\/p\u003e\n\n\u003ch2 id=\"presentation\"\u003eHow Breast Cancer Shows Up During Pregnancy\u003c\/h2\u003e\n\u003cp\u003ePregnant patients with breast cancer may notice the same symptoms as non-pregnant patients — most commonly a palpable lump or nipple discharge. But diagnosis is often delayed. That is because pregnancy causes normal physiological changes to the breast, including engorgement, hypertrophy (enlargement), nipple discharge, and increased density of breast tissue. These changes can hide a tumor. As a result, women may be diagnosed at more advanced disease stages.\u003c\/p\u003e\n\n\u003cp\u003eThe authors strongly advise that any suspicious or palpable mass that persists for 2 weeks or longer during pregnancy should be investigated. This is true even though about 80% of breast lesions found during pregnancy turn out to be benign (non-cancerous).\u003c\/p\u003e\n\n\u003ch2 id=\"diagnosis\"\u003eDiagnosing Breast Cancer During Pregnancy\u003c\/h2\u003e\n\u003cp\u003eInvestigating a palpable mass in pregnancy includes three steps: clinical examination, imaging, and biopsy.\u003c\/p\u003e\n\n\u003ch3\u003eLocal Staging (Checking the Breast and Lymph Nodes)\u003c\/h3\u003e\n\u003cp\u003eBreast ultrasound, including the axillary area (the armpit, where lymph nodes sit), is the first imaging choice. Ultrasound does not use ionizing radiation, and it can immediately identify obvious benign lesions such as cysts and galactoceles (milk-filled cysts) that need no further evaluation. For suspicious lesions, a biopsy may be performed.\u003c\/p\u003e\n\n\u003cp\u003eThe combined sensitivity (ability to correctly identify cancer) and specificity (ability to correctly rule out cancer) of ultrasound for detecting malignancy in pregnancy are \u003cstrong\u003e80.1%\u003c\/strong\u003e and \u003cstrong\u003e88.4%\u003c\/strong\u003e, respectively.\u003c\/p\u003e\n\n\u003cp\u003eAn initial mammogram may also be obtained, using either a single mediolateral oblique view (MLO, an angled side view) or a two-view approach (MLO plus cranio-caudal, a top-to-bottom view). Disease stage should be assessed using the American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) staging system. Ultrasound is combined with mammography using cranio-caudal and mediolateral oblique views of both breasts. This assesses tumor extent, multifocality, or bilateral disease. Multifocality means more than one tumor focus in the same breast. Bilateral disease means cancer in both breasts.\u003c\/p\u003e\n\n\u003cp\u003eThe additional detection gained by combining ultrasound and mammography is comparable to contrast-enhanced breast MRI: \u003cstrong\u003e15.5%\u003c\/strong\u003e cancer detection in the same breast and \u003cstrong\u003e3.9%\u003c\/strong\u003e in the opposite breast. Ultrasound is also used to assess regional lymph node status, and suspicious nodes can be confirmed by fine-needle aspiration or biopsy. In general, contrast-enhanced breast MRI may be omitted during pregnancy.\u003c\/p\u003e\n\n\u003ch4\u003eThe Question of MRI and Gadolinium Contrast\u003c\/h4\u003e\n\u003cp\u003eOutside of pregnancy, a contrast-enhanced MRI scan is considered for familial breast cancer associated with BRCA mutations. A contrast-enhanced MRI scan is also considered for lobular cancer, dense breast tissue, or suspected multicentricity or multifocality. A contrast-enhanced MRI scan is considered before neoadjuvant therapy, which is treatment given before surgery. A contrast-enhanced MRI scan is considered when findings are inconclusive or conflicting.\u003c\/p\u003e\n\n\u003cp\u003eDuring pregnancy, however, gadolinium-based contrast enhancement (a metal-based dye used to sharpen MRI images) is controversial. There are no known teratogenic effects of these agents in humans, but the U.S. Food and Drug Administration classifies them as pregnancy category C. Gadolinium-based contrast agents cross the placenta and enter the fetal circulation. After being excreted in urine, small quantities remaining in the amniotic fluid may dissociate into potentially toxic free gadolinium ions, with unclear long-term effects on the fetus.\u003c\/p\u003e\n\n\u003cp\u003eTherefore, contrast-enhanced MRI is possible but should be performed during pregnancy only when it will change clinical decision-making and postponing until after delivery is not an option. When it is used, the lowest dose possible of gadolinium should be given.\u003c\/p\u003e\n\n\u003ch3\u003eDistant Staging (Checking for Spread)\u003c\/h3\u003e\n\u003cp\u003eAs outside pregnancy, further staging should only be done in high-risk early breast cancer. This includes clinically positive axillary nodes, large tumors (5 cm or more), aggressive tumor biology, and clinical signs, symptoms, or laboratory values suggesting metastatic disease (cancer that has spread). In those situations, a chest CT scan, abdominal imaging, and a bone scan are considered.\u003c\/p\u003e\n\n\u003cp\u003ePET\/CT scans (positron emission tomography combined with computed tomography) may replace traditional imaging, but they may be less sensitive in lobular cancers and low-grade tumors.\u003c\/p\u003e\n\n\u003cp\u003eDuring pregnancy, ultrasound and MRI are the preferred imaging modalities because they involve no ionizing radiation and perform very accurately. Ionizing radiation imaging can be selectively performed in unresolved cases. Ionizing radiation imaging includes CT and PET\/CT. This is done when the benefit for the mother outweighs the risk to the fetus. This is done when the results will change clinical management and cannot be postponed. Radiation doses should be kept as low as reasonably achievable, and cumulative fetal radiation exposure over 100 mGy should be avoided.\u003c\/p\u003e\n\n\u003cp\u003eFetal exposure to ionizing radiation, and the related fetal risks, depend on gestational age, radiation dose, exposure time, and, where applicable, the radionuclide used.\u003c\/p\u003e\n\n\u003ch2 id=\"radiation\"\u003eUnderstanding Radiation Risk to the Fetus\u003c\/h2\u003e\n\u003cp\u003eThe authors describe two categories of radiation harm. The timing and size of the risk matter enormously.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eDeterministic effects\u003c\/strong\u003e (harm that occurs only above a threshold dose) such as miscarriage, growth restriction, congenital malformations, microcephaly (abnormally small head), or impaired fetal development can occur when fetal exposure exceeds a threshold of \u003cstrong\u003e100 to 200 mGy\u003c\/strong\u003e. In general, radiation's influence on pregnancy may include fetal death in the first 2 weeks after conception, malformations up to 2 months, and IQ decrease between the 3rd and 6th month.\u003c\/p\u003e\n\n\u003cp\u003eFrom 8 to 15 weeks of gestation, the fetus is most susceptible to radiation-induced mental retardation. There is a reduction of \u003cstrong\u003e21 IQ points per 1,000 mGy\u003c\/strong\u003e above a threshold of about 50 mGy. From 16 to 25 weeks, the reduction is \u003cstrong\u003e13 IQ points per 100 mGy\u003c\/strong\u003e above a threshold of about 50 mGy. After 25 weeks, no clear relationship has been described.\u003c\/p\u003e\n\n\u003cp\u003eImportantly, radiation doses from routine diagnostic exams are up to 100 times lower than these thresholds. Extra caution about cumulative fetal radiation exposure is needed when multiple imaging studies are required, so the threshold is not inadvertently exceeded.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eStochastic effects\u003c\/strong\u003e (random, unpredictable effects) are oncogenic or mutagenic effects of radiation exposure that have no safe threshold. The carcinogenic risk appears highest during the first trimester. A fetal exposure of 10 to 20 mGy may increase the background risk of childhood leukemia by a factor of 1.5 to 2.0, over a background rate of approximately 1 in 3,000.\u003c\/p\u003e\n\n\u003cp\u003eOnly direct exposure within the radiation field adds to fetal risk. Indirect fetal exposure from scatter radiation is negligible. This means abdominal shielding during radiography or CT is not necessary — and might even increase internal scatter.\u003c\/p\u003e\n\n\u003ch3\u003eHow Much Radiation Do Different Scans Deliver?\u003c\/h3\u003e\n\u003cp\u003eFor context, annual background radiation is 1.1 to 2.5 mGy. The table below shows typical fetal radiation doses from different techniques.\u003c\/p\u003e\n\n\u003ctable\u003e\n  \u003ctr\u003e\n\u003cth\u003eImaging technique\u003c\/th\u003e\n\u003cth\u003eFetal radiation dose (mGy)\u003c\/th\u003e\n\u003c\/tr\u003e\n  \u003ctr\u003e\n\u003ctd\u003eChest X-ray\u003c\/td\u003e\n\u003ctd\u003eless than 0.01\u003c\/td\u003e\n\u003c\/tr\u003e\n  \u003ctr\u003e\n\u003ctd\u003eMammography (two planes, bilateral)\u003c\/td\u003e\n\u003ctd\u003e0.001 to 0.01\u003c\/td\u003e\n\u003c\/tr\u003e\n  \u003ctr\u003e\n\u003ctd\u003eCT of the head\u003c\/td\u003e\n\u003ctd\u003eless than 0.005 to 0.5\u003c\/td\u003e\n\u003c\/tr\u003e\n  \u003ctr\u003e\n\u003ctd\u003eCT of the chest\u003c\/td\u003e\n\u003ctd\u003eless than 0.01 to 0.66\u003c\/td\u003e\n\u003c\/tr\u003e\n  \u003ctr\u003e\n\u003ctd\u003eCT of the abdomen\u003c\/td\u003e\n\u003ctd\u003e1.3 to 35\u003c\/td\u003e\n\u003c\/tr\u003e\n  \u003ctr\u003e\n\u003ctd\u003eCT of the pelvis\u003c\/td\u003e\n\u003ctd\u003e10 to 50\u003c\/td\u003e\n\u003c\/tr\u003e\n  \u003ctr\u003e\n\u003ctd\u003eLow-dose perfusion scintigraphy\u003c\/td\u003e\n\u003ctd\u003e0.1 to 0.5\u003c\/td\u003e\n\u003c\/tr\u003e\n  \u003ctr\u003e\n\u003ctd\u003e99mTc-bone scintigraphy\u003c\/td\u003e\n\u003ctd\u003e3.3\u003c\/td\u003e\n\u003c\/tr\u003e\n  \u003ctr\u003e\n\u003ctd\u003e18F-FDG PET whole-body scintigraphy\u003c\/td\u003e\n\u003ctd\u003e1.1 to 990\u003c\/td\u003e\n\u003c\/tr\u003e\n  \u003ctr\u003e\n\u003ctd\u003e18F-FDG PET\/CT whole-body scintigraphy\u003c\/td\u003e\n\u003ctd\u003e10 to 50\u003c\/td\u003e\n\u003c\/tr\u003e\n  \u003ctr\u003e\n\u003ctd\u003e18F-FDG PET\/MRI whole-body scintigraphy\u003c\/td\u003e\n\u003ctd\u003e3.334\u003c\/td\u003e\n\u003c\/tr\u003e\n\u003c\/table\u003e\n\n\u003cp\u003eRadiation doses may vary depending on the characteristics of the imaging device and technique used, and doses have decreased in recent decades for different imaging modalities. For nuclear studies, fetal exposure also depends on the physical and biochemical properties of the nuclide.\u003c\/p\u003e\n\n\u003cp\u003eTo put the units in plain terms: exposure is measured in Roentgen, which is ions produced per kilogram of air. Dose is measured in rad or Gray, which is energy deposited per kilogram of tissue. 1 Gy equals 100 rad, and 1 Gy equals 1,000 mGy. Relative effective dose is measured in rem or Sievert, which is energy deposited normalized for biological effectiveness. 1 Sv equals 100 rem. For diagnostic X-rays, 1 rad equals 1 rem and 1 Gy equals 1 Sv.\u003c\/p\u003e\n\n\u003ch3\u003eAlternatives to Standard Staging Scans\u003c\/h3\u003e\n\u003cp\u003eWhole-body diffusion-weighted MRI can be used for staging when available. Recent studies show excellent diagnostic performance for detecting distant metastases (including skeletal, liver, and peritoneal spread) and lymph node metastases in pregnant cancer patients. These studies also showed high agreement between different readers, an accuracy of \u003cstrong\u003e90%\u003c\/strong\u003e for primary tumor detection, \u003cstrong\u003e98.5% to 99.5%\u003c\/strong\u003e for detecting nodal metastases, and \u003cstrong\u003e90% to 100%\u003c\/strong\u003e for detecting distant metastases.\u003c\/p\u003e\n\n\u003cp\u003eIn nuclear imaging, the two most commonly used tracers — 18F-fluorodeoxyglucose (FDG) and technetium (Tc-99m) — may be used safely in pregnant patients. Several measures can minimize fetal radiation dose during nuclear imaging:\u003c\/p\u003e\n\u003col\u003e\n  \u003cli\u003eCareful dose calculation that accounts for physiological changes in pregnancy.\u003c\/li\u003e\n  \u003cli\u003eUse of a bladder catheter together with intravenous hydration, to avoid accumulation of tracer in the maternal bladder.\u003c\/li\u003e\n  \u003cli\u003eAdjustment of scanning time.\u003c\/li\u003e\n\u003c\/ol\u003e\n\n\u003cp\u003eHowever, standard use of hybrid imaging with CT will increase cumulative fetal radiation exposure. As an alternative, PET\/MRI is a promising development with improved detection of distant metastases compared with PET\/CT. So far, this technique has only been specifically investigated in a small series of pregnant cancer patients, where it resulted in a very low fetal radiation dose of \u003cstrong\u003e3.3 mGy\u003c\/strong\u003e.\u003c\/p\u003e\n\n\u003ch2 id=\"phenotypes\"\u003eTumor Types and Biology\u003c\/h2\u003e\n\u003cp\u003ePathological diagnosis should be based on core needle biopsy, according to the World Health Organization (WHO) classification and AJCC TNM staging system. Breast cancer is classified into stages 0 through IV. Staging includes prognostic information about tumor biology. This includes tumor grade, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). This also includes Ki-67, a marker of how fast cells divide, and gene expression data when applicable.\u003c\/p\u003e\n\n\u003cp\u003eGene expression analysis can sort breast cancer into four types:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003e\n\u003cstrong\u003eLuminal A:\u003c\/strong\u003e ER-positive, PR-positive, HER2-negative, low Ki67.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eLuminal B:\u003c\/strong\u003e ER-positive, PR-positive, either HER2-negative or HER2-positive, high Ki67.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eHER2-enriched:\u003c\/strong\u003e ER-negative, PR-negative, HER2-positive.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eBasal-like:\u003c\/strong\u003e ER-negative, PR-negative, HER2-negative (also called triple-negative).\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003eBreast cancer during pregnancy resembles the phenotypes most commonly found in young breast cancer patients. These are mainly high-grade invasive carcinomas not otherwise specified (NOS). These carcinomas often have characteristics associated with aggressive behavior and larger tumors. These carcinomas also have a higher incidence of positive nodes and lymphvascular invasion. Lymphvascular invasion means cancer cells inside lymph or blood vessels.\u003c\/p\u003e\n\n\u003ch3\u003eHow Pregnant and Non-Pregnant Patients Compare\u003c\/h3\u003e\n\u003cp\u003eA large cohort drawn from two registries (INCIP and the German Breast Group) compared 662 pregnant cancer patients with 1,082 non-pregnant cancer patients, all aged up to 45 years. Pregnant patients were more likely to have:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003eStage II breast cancer: \u003cstrong\u003e60.1% vs 56.1%\u003c\/strong\u003e (p=0.035, statistically significant).\u003c\/li\u003e\n  \u003cli\u003eGrade 3 tumors: \u003cstrong\u003e74.0% vs 62.2%\u003c\/strong\u003e (p\u0026lt;0.001, highly significant).\u003c\/li\u003e\n  \u003cli\u003eHormone receptor-negative tumors: \u003cstrong\u003e48.4% vs 34.0%\u003c\/strong\u003e (p\u0026lt;0.001).\u003c\/li\u003e\n  \u003cli\u003eTriple-negative breast cancer: \u003cstrong\u003e38.9% vs 26.9%\u003c\/strong\u003e (p\u0026lt;0.001).\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003eHER2 was positive in 29.2% of pregnant patients, a difference that was not statistically significant.\u003c\/p\u003e\n\n\u003cp\u003eWhen broken down by biological subtype, breast cancer during pregnancy is less often luminal A and more often triple-negative:\u003c\/p\u003e\n\n\u003ctable\u003e\n  \u003ctr\u003e\n\u003cth\u003eSubtype\u003c\/th\u003e\n\u003cth\u003ePregnant patients\u003c\/th\u003e\n\u003cth\u003eNon-pregnant patients\u003c\/th\u003e\n\u003c\/tr\u003e\n  \u003ctr\u003e\n\u003ctd\u003eMedian age\u003c\/td\u003e\n\u003ctd\u003e34\u003c\/td\u003e\n\u003ctd\u003e38\u003c\/td\u003e\n\u003c\/tr\u003e\n  \u003ctr\u003e\n\u003ctd\u003eLuminal A (HER2-negative, hormone receptor-positive, low Ki67)\u003c\/td\u003e\n\u003ctd\u003e10.8% to 13.7%\u003c\/td\u003e\n\u003ctd\u003e24.0% to 50.9%\u003c\/td\u003e\n\u003c\/tr\u003e\n  \u003ctr\u003e\n\u003ctd\u003eLuminal B (HER2-negative, hormone receptor-positive, high Ki67)\u003c\/td\u003e\n\u003ctd\u003e18.2% to 38.4%\u003c\/td\u003e\n\u003ctd\u003e20.1% to 21.1%\u003c\/td\u003e\n\u003c\/tr\u003e\n  \u003ctr\u003e\n\u003ctd\u003eHER2-positive\u003c\/td\u003e\n\u003ctd\u003e15.8% to 29.2%\u003c\/td\u003e\n\u003ctd\u003e8.0% to 27.2%\u003c\/td\u003e\n\u003c\/tr\u003e\n  \u003ctr\u003e\n\u003ctd\u003eBasal-like \/ triple-negative\u003c\/td\u003e\n\u003ctd\u003e30.1% to 38.9%\u003c\/td\u003e\n\u003ctd\u003e17.4% to 26.9%\u003c\/td\u003e\n\u003c\/tr\u003e\n\u003c\/table\u003e\n\n\u003ch3\u003eMolecular Differences\u003c\/h3\u003e\n\u003cp\u003eThe most commonly mutated genes in breast cancer patients are TP53 and PIK3CA, with no significant differences between pregnant and non-pregnant patients. However, other molecular characteristics do differ. Pregnancy-related breast cancer shows a higher frequency of mutations in the mucin gene family and an enrichment of mismatch repair deficiency mutational signature.\u003c\/p\u003e\n\n\u003cp\u003eThe mucin gene family plays a major role in glycosylation mechanisms (the process by which sugars are attached to proteins). Alterations in the biological functions of glycosylation are correlated with breast carcinogenesis (the development of breast cancer) and metastasis (spread).\u003c\/p\u003e\n\n\u003cp\u003eA recent systematic review summarized all available data on the genomic background and gene mutation patterns of pregnancy-associated breast cancer compared with non-pregnant patients. The review found aberrant (abnormal) expression of several groups of genes:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003eOncogenes, such as MYC, FOS, and MUC1.\u003c\/li\u003e\n  \u003cli\u003eApoptosis regulators (genes controlling programmed cell death).\u003c\/li\u003e\n  \u003cli\u003eTranscription regulators.\u003c\/li\u003e\n  \u003cli\u003eGenes involved in DNA repair mechanisms, such as Sig20 and BRCA1.\u003c\/li\u003e\n  \u003cli\u003eGenes involved in cell proliferation, such as IGF1 and MKI67.\u003c\/li\u003e\n  \u003cli\u003eGenes involved in immune response, such as PD1 and PDL1.\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003eIn contrast, the most down-regulated genes were tumor suppressor genes (TP53 and PTEN). The most down-regulated genes also included cell cycle regulator genes (BCL2). The most down-regulated genes also included genes involved in DNA repair mechanisms. The most down-regulated genes also included genes involved in protein modification and transport. Researchers hypothesize that these features may promote tumor progression during pregnancy or postpartum breast cancer, with distinct differences between breast cancer during pregnancy and postpartum breast cancer.\u003c\/p\u003e\n\n\u003ch2 id=\"treatment\"\u003eTreatment Principles: The Big Picture\u003c\/h2\u003e\n\u003cp\u003eThe aim of treatment is the best possible oncological outcome for the pregnant patient. Physicians should therefore adhere to the standard of care for non-pregnant patients whenever possible.\u003c\/p\u003e\n\n\u003cp\u003ePatient and tumor characteristics, stage, gestational age, and the wishes of the patient and her partner concerning the pregnancy all guide therapeutic strategy. It should be clear whether treatment is curative or palliative (aimed at relieving symptoms rather than curing), and which treatment modality is most appropriate to prioritize first. The prognosis will naturally affect decisions about continuing the pregnancy.\u003c\/p\u003e\n\n\u003cp\u003eA multidisciplinary team should assess and weigh the medical (obstetrical), oncological, radiotherapeutic, pediatric, molecular and clinical genetic, ethical, and psychological issues. The patient and her partner need careful counselling on treatment options, maternal and fetal risk, and decisions about continuing or terminating the pregnancy.\u003c\/p\u003e\n\n\u003cp\u003eCrucially, \u003cstrong\u003etermination of pregnancy has not been shown to improve outcome\u003c\/strong\u003e. Premature delivery, or unnecessary delay in diagnosis or treatment in order to start treatment after delivery, should therefore be avoided. Prematurity can often be minimized by starting cancer treatment during pregnancy.\u003c\/p\u003e\n\n\u003cp\u003eBased on the review's overall findings, the treatment modalities break down as follows:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003e\n\u003cstrong\u003eSurgery\u003c\/strong\u003e is possible during all trimesters.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eRadiotherapy\u003c\/strong\u003e is possible during pregnancy in the first half of pregnancy.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eChemotherapy\u003c\/strong\u003e can be safely administered starting from 12 weeks of gestational age.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eEndocrine therapy\u003c\/strong\u003e (hormone-blocking treatment) and \u003cstrong\u003eHER2-targeted therapy\u003c\/strong\u003e are contraindicated throughout the whole pregnancy.\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003ch2 id=\"surgery\"\u003eSurgery During Pregnancy\u003c\/h2\u003e\n\u003cp\u003eBreast cancer surgery can be performed safely during any stage of pregnancy. Currently used anesthetics in standard concentrations are not known to have any teratogenic effects (effects that cause birth defects). How much anesthetic medication crosses the placenta depends on its lipophilicity (fat solubility), degree of ionization, molecular mass, and protein binding.\u003c\/p\u003e\n\n\u003cp\u003eThe timing of surgery should be determined based on patient and tumor characteristics, gestational age, and preferences. Elective surgery should be postponed until after delivery.\u003c\/p\u003e\n\n\u003cp\u003eIn general, the risks of surgery during pregnancy include preterm delivery, miscarriage, and fetal distress. However, in non-abdominal surgery these risks are small. Adequate maternal care during the perioperative period (around the time of surgery) is most important for fetal well-being.\u003c\/p\u003e\n\n\u003cp\u003eSpecific precautions the authors highlight:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003ePosition the patient in a left lateral tilt after 20 weeks of gestation, to optimize vena cava volume (blood flow back to the heart).\u003c\/li\u003e\n  \u003cli\u003ePrevent hypoxia (low oxygen), hypotension (low blood pressure), hypoglycemia (low blood sugar), fever, pain, infections, and thrombosis (blood clots), because these can harm fetal health and development.\u003c\/li\u003e\n  \u003cli\u003eUnderstand that placental perfusion depends primarily on maternal blood pressure and lacks autoregulation. Maternal hypotension from hemorrhage or hypovolemia (low blood volume) may therefore decrease perfusion and cause fetal hypoxia.\u003c\/li\u003e\n  \u003cli\u003eGive appropriate thromboprophylaxis with low molecular weight heparin (LMWH) to reduce the risk of venous thromboembolic events (blood clots in the veins).\u003c\/li\u003e\n  \u003cli\u003eTreat pain adequately, because excessive pain may trigger preterm labor.\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003eMonitoring the fetal heart rate (FHR) by cardiotocography (CTG) during surgery is debatable. CTG is a continuous electronic recording of the baby's heartbeat and contractions. But monitoring the fetal heart rate can help detect fetal distress. This depends on gestational age and potential viability. If fetal monitoring is used, the authors recommend performing surgery at an institution with neonatal and pediatric services and having an obstetric care provider readily available. Obstetricians should be aware that FHR patterns will be influenced by anesthesia and surgery. Even so, a CTG before and after a procedure is a minimum requirement. If there are signs of fetal distress, staff should consider repositioning the pregnant patient and giving fluid replacement and oxygen, among other measures.\u003c\/p\u003e\n\n\u003ch3\u003eMedications Considered Safe Around Surgery\u003c\/h3\u003e\n\u003cp\u003eThe review lists medications that can be used safely during surgery. These include desflurane, propofol, opiates (sufentanil up to 30 mg and morphine), lidocaine, ketamine, peri-operative anti-emetics (ondansetron, metoclopramide, granisetron), steroids (hydrocortisone, methylprednisolone, prednisolone, dexamethasone), and proton pump inhibitors.\u003c\/p\u003e\n\n\u003cp\u003eDiscouraged medications are NSAIDs (non-steroidal anti-inflammatory drugs, except when used as an anti-tocolytic drug to stop contractions) and metamizole. Methylprednisolone, hydrocortisone, and prednisolone are preferred because they are actively metabolized in the placenta, leaving lower concentrations in the fetus.\u003c\/p\u003e\n\n\u003ch3\u003eChoosing the Operation\u003c\/h3\u003e\n\u003cp\u003eThe choice of breast cancer surgery during pregnancy should follow the same guidelines as for non-pregnant women, favoring breast-conserving therapy when feasible. If immediate breast reconstruction is considered, prosthetic implants are possible. But autologous reconstruction is delayed until after delivery. Autologous reconstruction uses the patient's own tissue. In any case, physiological alterations are taken into account.\u003c\/p\u003e\n\n\u003cp\u003eThe need for radiotherapy after breast-conserving surgery should not be used as an argument to favor mastectomy, because radiotherapy may start after delivery.\u003c\/p\u003e\n\n\u003ch2 id=\"safety\"\u003eSentinel Lymph Node Staging and Medication Safety\u003c\/h2\u003e\n\u003cp\u003eSentinel lymph node staging (a procedure that identifies and tests the first lymph node cancer would likely spread to) can safely be performed during pregnancy. In a study of premenopausal non-pregnant patients, peritumoral injection of 12 MBq of 99m-Tc was performed. The radiotracer was found only at the injection site and in the sentinel node. None of the radiotracer was traceable in the abdomen. Safety was confirmed in another study of 25 pregnant patients using 99m-Tc and\/or methylene blue.\u003c\/p\u003e\n\n\u003cp\u003eOne important caution: if a sentinel lymph node procedure is performed, the blue dye (Patent Blue®) should be avoided. It carries a small risk of an anaphylactic maternal reaction (a severe allergic reaction) and subsequent fetal distress.\u003c\/p\u003e\n\n\u003ch2 id=\"implications\"\u003eWhat This Means for Patients\u003c\/h2\u003e\n\u003cp\u003eThe central message of this review is reassuring but demanding. Pregnancy is not a reason to delay or water down cancer treatment. In most cases, women can be treated aggressively while continuing their pregnancy.\u003c\/p\u003e\n\n\u003cp\u003eThe practical consequences for patients are specific:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003eYou may receive chemotherapy during pregnancy, but not before 12 weeks of gestation.\u003c\/li\u003e\n  \u003cli\u003eYou can have breast surgery in any trimester, including sentinel lymph node testing.\u003c\/li\u003e\n  \u003cli\u003eYou cannot receive hormone-blocking therapy or HER2-targeted therapy while pregnant — these must wait until after delivery.\u003c\/li\u003e\n  \u003cli\u003eUltrasound and MRI are the preferred imaging tools; CT and PET\/CT are used only when the benefit clearly outweighs the fetal risk.\u003c\/li\u003e\n  \u003cli\u003eFetal growth should be monitored throughout, and long-term follow-up of children is encouraged in dedicated centers.\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003eBecause breast cancer during pregnancy is more often triple-negative and higher grade than breast cancer in non-pregnant women of similar age, prompt diagnosis matters. A lump that persists beyond 2 weeks deserves imaging and, if needed, a biopsy — even though 8 in 10 such lumps turn out to be benign.\u003c\/p\u003e\n\n\u003cp\u003eThe authors also emphasize that delivering the baby early purely to begin treatment is usually the wrong move. Prematurity carries its own serious risks, and starting cancer treatment during pregnancy often reduces the need for early delivery.\u003c\/p\u003e\n\n\u003ch2 id=\"limitations\"\u003eLimitations of the Evidence\u003c\/h2\u003e\n\u003cp\u003eThis is a review article, not a new clinical trial. Several important gaps remain.\u003c\/p\u003e\n\n\u003cp\u003eRandomized trials in pregnant cancer patients are not feasible for ethical reasons. Most evidence comes from registries and cohort studies, such as the INCIP cohort of 1,170 patients and the combined INCIP\/German Breast Group cohort of 662 pregnant and 1,082 non-pregnant patients.\u003c\/p\u003e\n\n\u003cp\u003eThe safety of PET\/MRI has only been investigated in a small series of pregnant cancer patients, despite its promising low fetal radiation dose of 3.3 mGy. The long-term effects of free gadolinium ions that may remain in amniotic fluid are still unclear. And while antenatal chemotherapy was associated with more small-for-gestational-age neonates and NICU admissions, the reasons for this association are not fully settled.\u003c\/p\u003e\n\n\u003ch2 id=\"recommendations\"\u003ePractical Recommendations\u003c\/h2\u003e\n\u003cp\u003eBased on this review, patients and clinicians should consider the following steps:\u003c\/p\u003e\n\n\u003col\u003e\n  \u003cli\u003eReport any breast lump or nipple discharge that lasts 2 weeks or more during pregnancy. Do not assume it is just a pregnancy change.\u003c\/li\u003e\n  \u003cli\u003eAsk for breast ultrasound as the first imaging test. It is safe and accurate in pregnancy.\u003c\/li\u003e\n  \u003cli\u003eRequest a referral for genetic counselling, since young age at diagnosis makes inherited mutations more likely.\u003c\/li\u003e\n  \u003cli\u003eAsk to be managed by a multidisciplinary team with expertise in cancer during pregnancy. Dedicated advisory boards exist for exactly this purpose.\u003c\/li\u003e\n  \u003cli\u003eDiscuss the full sequence and timing of surgery, radiotherapy, and chemotherapy with your team before making decisions about delivery timing.\u003c\/li\u003e\n  \u003cli\u003eEnsure fetal growth is monitored during treatment and arrange long-term pediatric follow-up after birth.\u003c\/li\u003e\n\u003c\/ol\u003e\n\n\u003cp\u003eThe authors' bottom line is clear. Pregnancy should be maintained as long as possible, treatment should not be delayed, and every decision should be individualized by a multidisciplinary team weighing maternal, fetal, and family considerations together.\u003c\/p\u003e\n\n\u003c!-- ddn:faq:start --\u003e\n\u003ch2 id=\"ddn-faq\"\u003eFrequently Asked Questions\u003c\/h2\u003e\n\u003ch3\u003eI'm pregnant and found a breast lump. How likely is it to be cancer?\u003c\/h3\u003e\n\u003cp\u003eAbout 80% of breast lesions found during pregnancy turn out to be benign (non-cancerous). However, any suspicious or palpable mass that persists for 2 weeks or longer should be investigated. Diagnosis is often delayed because normal pregnancy changes—engorgement, enlargement, nipple discharge, and increased breast density—can hide a tumor, so women may be diagnosed at more advanced stages.\u003c\/p\u003e\n\u003ch3\u003eWhat tests are used to diagnose breast cancer during pregnancy?\u003c\/h3\u003e\n\u003cp\u003eInvestigation includes clinical examination, imaging, and biopsy. Breast ultrasound, including the axillary area, is the first imaging choice because it uses no ionizing radiation and can identify benign cysts. An initial mammogram may also be obtained. For suspicious lesions, a core needle biopsy is performed. Contrast-enhanced breast MRI may generally be omitted during pregnancy.\u003c\/p\u003e\n\u003ch3\u003eCan I have surgery for breast cancer while pregnant?\u003c\/h3\u003e\n\u003cp\u003eYes. Breast cancer surgery can be performed safely during any trimester. Currently used anesthetics in standard concentrations are not known to have teratogenic effects. Sentinel lymph node staging can also be safely performed during pregnancy. But the blue dye Patent Blue® should be avoided. Patent Blue® carries a small risk of maternal anaphylaxis and fetal distress.\u003c\/p\u003e\n\u003ch3\u003eCan I receive chemotherapy during pregnancy?\u003c\/h3\u003e\n\u003cp\u003eChemotherapy can be safely administered starting from 12 weeks of gestational age. It cannot be given before 12 weeks. In a study of 1,170 patients, 67% received cancer treatment during pregnancy, and the likelihood increased over time mainly due to greater chemotherapy use. However, antenatal chemotherapy was associated with more small-for-gestational-age neonates and NICU admissions.\u003c\/p\u003e\n\u003ch3\u003eAre hormone therapy and HER2-targeted therapy safe during pregnancy?\u003c\/h3\u003e\n\u003cp\u003eNo. Endocrine (hormone-blocking) therapy and HER2-targeted therapy are contraindicated throughout the whole pregnancy. These treatments must wait until after delivery. Surgery is possible in all trimesters. Radiotherapy is possible in the first half of pregnancy. Chemotherapy can be given from 12 weeks. But hormone and HER2-targeted therapies cannot be used while pregnant.\u003c\/p\u003e\n\u003ch3\u003eWhat is the risk of radiation to my baby from scans?\u003c\/h3\u003e\n\u003cp\u003eRadiation doses from routine diagnostic exams are up to 100 times lower than the 100–200 mGy threshold for deterministic effects like malformations. A fetal exposure of 10–20 mGy may increase the background risk of childhood leukemia by a factor of 1.5–2.0, over a background rate of about 1 in 3,000. Ultrasound and MRI are preferred because they use no ionizing radiation.\u003c\/p\u003e\n\u003ch3\u003eShould I deliver early to start cancer treatment?\u003c\/h3\u003e\n\u003cp\u003eNo. Delivering the baby early purely to begin treatment is usually the wrong move. Prematurity carries its own serious risks, and starting cancer treatment during pregnancy often reduces the need for early delivery. Termination of pregnancy has not been shown to improve outcome. Pregnancy should be maintained as long as possible while treatment proceeds without delay.\u003c\/p\u003e\n\u003ch3\u003eWhen should a patient diagnosed with breast cancer during pregnancy seek a second opinion?\u003c\/h3\u003e\n\u003cp\u003eBreast cancer during pregnancy is rare. Treatment is a balancing act between maternal and fetal safety. A second opinion is reasonable when the plan does not clearly follow standard care. Standard care is surgery in any trimester and radiotherapy in the first half of pregnancy. Standard care is chemotherapy from 12 weeks and no endocrine or HER2-targeted therapy while pregnant. It is also worth seeking review if diagnosis was delayed, if early delivery is proposed mainly to start treatment, or if the tumor is triple-negative. A multidisciplinary team should weigh the sequence and timing of each modality. Diagnostic Detectives Network provides independent expert second opinions.\u003c\/p\u003e\n\u003c!-- ddn:faq:end --\u003e\n\n\u003ch2 id=\"source\"\u003eSource Information\u003c\/h2\u003e\n\u003cp\u003e\u003cstrong\u003eOriginal article title:\u003c\/strong\u003e Breast cancer during pregnancy- epidemiology, phenotypes, presentation during pregnancy and therapeutic modalities\u003c\/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors:\u003c\/strong\u003e Ingrid Boere (medical oncologist), Christianne Lok (gynaecological oncologist), Philip Poortmans (radiation oncologist), Linetta Koppert (surgical oncologist), Rebecca Painter (obstetrical gynaecologist), Marry M. van den Heuvel-Eibrink (pediatric oncologist), and Frederic Amant (gynaecological oncologist)\u003c\/p\u003e\n\u003cp\u003e\u003cstrong\u003eAffiliations:\u003c\/strong\u003e Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, the Netherlands; Center for Gynecological Oncology Amsterdam (CGOA), Antoni van Leeuwenhoek Netherlands Cancer Institute, Amsterdam, the Netherlands; Iridium Network and University of Antwerp, Faculty of Medicine and Health Sciences, Wilrijk-Antwerp, Belgium; Department of Obstetrics and Gynecology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands; Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands; Gynecologic Oncology, UZ Leuven, Belgium\u003c\/p\u003e\n\u003cp\u003e\u003cstrong\u003ePublication:\u003c\/strong\u003e Best Practice \u0026amp; Research Clinical Obstetrics and Gynaecology, volume 82 (2022), pages 46–59\u003c\/p\u003e\n\u003cp\u003e\u003cstrong\u003eArticle history:\u003c\/strong\u003e Received 21 April 2022; received in revised form 2 May 2022; accepted 2 May 2022\u003c\/p\u003e\n\u003cp\u003e\u003cstrong\u003eDOI:\u003c\/strong\u003e 10.1016\/j.bpobgyn.2022.05.001\u003c\/p\u003e\n\u003cp\u003e\u003cstrong\u003eLicense:\u003c\/strong\u003e © 2022 The Author(s). Published by Elsevier Ltd. Open access under the CC BY license.\u003c\/p\u003e\n\u003cp\u003e\u003cem\u003eThis patient-friendly article is based on peer-reviewed research.\u003c\/em\u003e\u003c\/p\u003e","brand":"DiagnosticDetectives.Com","offers":[{"title":"Default Title","offer_id":47545194741916,"sku":null,"price":0.0,"currency_code":"USD","in_stock":true}],"thumbnail_url":"\/\/cdn.shopify.com\/s\/files\/1\/0599\/5449\/5644\/files\/ddn-medical-article-breast-cancer-during-pregnancy-a-comprehensive-guide-to-diagnosis-treatment-and-safety-for-mother-and-baby-hero.png?v=1790156023","url":"https:\/\/diagnosticdetectives.com\/he\/products\/breast-cancer-during-pregnancy-a-comprehensive-guide-to-diagnosis-treatment-and-safety-for-mother-and-baby","provider":"DiagnosticDetectives.Com","version":"1.0","type":"link"}