Ultrasonography is the first line imaging modality for evaluation of a breast mass during pregnancy because it can differentiate between solid and cystic lesions and lacks ionizing radiation, which may be associated with birth defects. In several studies, ultrasonography had an extremely high sensitivity in the detection of BCDP and detected both benign and malignant lesions. Robbins et al. Ultrasonography is generally recommended for evaluating breast lesions in women younger than age 30 years because of increased breast density in this age group.
However, in the dense breast of pregnancy, ultrasonography is appropriate at all ages. There is minimal risk to the developing fetus with mammography because of modern shielding techniques. Ionizing radiation exposure to the fetus is less than 0. Magnetic resonance imaging MRI with contrast is not recommended during pregnancy.
In breastfeeding women in the postpartum period, MRI with contrast may safely be performed; however, the images may be difficult to interpret given increased background enhancement from hypervascularity and lactational changes. The American College of Radiology endorses the safety of breastfeeding after MRI after potential risks have been discussed. If the mother remains concerned, it is recommended she refrain from breastfeeding for 12—24 hours after administration of gadolinium [ 21 ]. For advanced cancers, systemic staging studies are indicated. In the pregnant patient, staging studies should be performed only if they will change the treatment recommendations.
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Radionucleotide bone scanning with hydration and an indwelling catheter may be used when MRI is not available [ 22 ]. Surgical recommendations for women with BCDP are similar to recommendations for women who are not pregnant. Recommendations are based on the clinical stage, tumor biology, genetic status, gestational age, and surgical desires of the woman. Gestational age at diagnosis is an important element of surgical planning Table 2.
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Because BCDP commonly presents with locally advanced disease, systemic therapy has the potential advantage of treating both locoregional and distant disease. Neoadjuvant chemotherapy has an added benefit of potentially reducing the size of the cancer, making the patient a better candidate for breast conservation. Because BCDP patients are diagnosed at a young age, genetic testing is usually indicated.
Administration of neoadjuvant chemotherapy allows time for results to be interpreted to guide surgical planning. Historically, modified radical mastectomy was the standard of care for women diagnosed with BCDP. As will be discussed in detail later in this article, pregnant women cannot safely undergo radiation.
This previously precluded the use of breast conservation surgery in BCDP. Because many women will undergo chemotherapy as part of their treatment plan, this regimen will often extend until delivery, allowing for adjuvant radiation to be safely given postpartum. This paradigm shift has made it possible for BCDP patients to be candidates for breast conservation surgery without compromising their cancer treatment.
Kuerer et al. Several studies have documented the feasibility of lymphoscintigraphy during pregnancy and measured the uterine dose of radiation from lymphoscintigraphy for sentinel lymph node biopsy. Uterine radiation dose was calculated at 1. Sentinel lymph node biopsy should be considered standard of care for BCDP in the clinically negative axilla.
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The U. Anesthetic considerations for surgery during pregnancy include concern for the safety of two patients: the mother and the fetus. Alterations in maternal anatomy and physiology induced by pregnancy have clinical anesthetic implications and present potential hazards for the mother and fetus undergoing anesthesia.
The fetus may be subjected to hazard by a the risk for intraoperative hypoxemia or asphyxia caused by reduced uterine blood flow, maternal hypotension, excessive maternal mechanical ventilation or maternal hypoxia, and depression of the fetal cardiovascular system or central nervous system from placental passage of anesthetic agents; b exposure to teratogenic drugs; and c the risk for preterm delivery as a consequence of the surgical procedure or drugs administered [ 29 ].
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In most circumstances, the fetus is a passive recipient of anesthesia administered to the mother, suffers no blood loss, and undergoes passive changes rather than direct stress or hemodynamic alterations caused by surgery. Surgery can be safely performed at any time during pregnancy as long as certain issues are addressed.
Anesthetic considerations include the safety of both the mother and the fetus. A population study has suggested that adverse fetal outcomes after surgery may be due to the underlying maternal disease rather than the direct effect of anesthesia [ 30 ]. Although there is scant evidence of teratogenicity of commonly used anesthetic agents, surgery is not generally recommended until after the first trimester, when organogenesis is complete, in order to minimize potential risks to the developing fetus. Other considerations include maternal physiologic changes, such as hypercoagulability, delayed gastric emptying, increased blood volume and cardiac output, decreased functional residual capacity of the lungs, and decreased serum cholinesterase activity.
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The safest time to perform surgery during pregnancy is during the second trimester. During the third trimester, the greatest risk to the fetus is premature labor and premature delivery, which can be initiated by the stress of surgery. Obstetric and neonatologic care should be readily available, with access to a neonatal intensive care unit.
Surgery may then be performed postpartum. Timing of treatment initiation must be weighed against both the benefit of delivery after fetal maturity and the risk for neutropenia. Perioperative care of the pregnant patient should include continued close fetal monitoring. Narcotic pain medications are widely used during pregnancy. Dosage and duration should be closely monitored to minimize infant dependency.
For instance, pregnancy is associated with dramatic changes in blood volume, hepatic metabolism, and renal clearance, all of which can affect adequate delivery of chemotherapy . Perhaps one of the most important considerations in the selection and timing of systemic therapy is the effect of chemotherapy on fetal development. Following implantation approximately 2 weeks after conception, organogenesis occurs over the course of the next 8 to 10 weeks, at which time major malformations and fetal loss are most likely to occur [ 31 ].
Thus, chemotherapy is contraindicated during the first trimester of pregnancy. During the second and third trimesters, the use of cytotoxic chemotherapy is more widely accepted. The fetal and maternal outcomes of two notable studies—Hahn and colleagues updated by Murthy et al. Importantly, the German study results illustrate that although more complications were reported for infants exposed to chemotherapy in utero, complications were more common among infants born prematurely, irrespective of exposure to chemotherapy [ 42 ].
Taking these data into account, we recommend that the careful decision regarding timing of chemotherapy during pregnancy consider a standard clinicopathologic features i. On the basis of the available data, we would recommend initiation of systemic chemotherapy after completion of the first trimester, in the absence of a compelling contraindication.
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Data with other regimens and other classes of chemotherapy agents, including taxanes and platinum agents, are more limited [ 43 ], [ 44 ], [ 45 ], [ 46 ] Table 3. This difficult decision relies on weighing the risks and benefits to the patient and fetus.
In addition to type of chemotherapy, schedule of chemotherapy must also be considered. However, the use of growth factors i. As noted earlier, chemotherapy dosing in the pregnant patient should be the same as in the nonpregnant patient and should be based on actual body surface area calculation before every chemotherapy cycle [ 51 ]. Data regarding the safety of supportive drugs during pregnancy is relatively limited, and these medications should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus Table 4. The 5HT3 antagonists ondansetron, palonosetron, and granisetron are classified as pregnancy risk factor B.
Few [ 52 ] or no reports have addressed granisetron and palonosetron in human pregnancy, respectively, but animal studies indicate that the risk of these agents during pregnancy is low [ 53 ], [ 54 ]. Regarding ondansetron, several studies support that this 5HT3 antagonist is not associated with an increased risk for birth defects [ 55 ], [ 56 ], [ 57 ]. However, the FDA has issued a warning regarding an increased risk for cardiac arrhythmia i. No data in humans are available for neurokinin1 inhibitors i.
Limited animal data suggest the risk during pregnancy may be low. It is recommended to consider the dehydration and potential toxicity risks and use accordingly [ 61 ]. Animal and human studies with corticosteroids are conflicting but seem to suggest some increased risk for fetal risk, particularly in the first trimester. The benefits of corticosteroids are generally thought to outweigh the risks [ 62 ]. Prednisolone and hydrocortisone are preferred over dexamethasone because they are highly metabolized in the placenta and have limited penetration into the fetal compartment [ 63 ].
Antihistamines, H1 and H2 antagonists used to prevent allergic reactions with chemotherapy, are generally considered safe for use during pregnancy. It is the preferred parenteral H1 antagonist [ 65 ]. The H2 antagonists ranitidine, famotidine, and cimetidine pregnancy risk factor B have low potential for birth defects, as animal and human studies demonstrate [ 66 ]. Ranitidine is considered the drug of choice over famotidine and cimetidine.
Study found no significant differences in the birth outcomes including birth weight, preterm birth, newborn mean white blood counts, and congenital malformations between groups [ 49 ]. The FDA has categorized trastuzumab as a Category D drug because of updated safety information released in December Exposure to trastuzumab during pregnancy has been associated with oligohydramnios and oligohydramnios syndrome manifesting as pulmonary hypoplasia, skeletal abnormalities, renal insufficiency, and neonatal death.
These findings have been noted I reports and postmarketing experience with trastuzumab [ 67 ], [ 68 ], [ 69 ]. In the unfortunate case of trastuzumab exposure during pregnancy, treatment should be discontinued and the fetus should be closely monitored, with particular attention to amniotic fluid volumes. Pertuzumab, a monoclonal antibody that blocks the dimerization of HER2 and HER3, was approved by the FDA in the neoadjuvant setting in based on higher pathologic complete response rates for patients receiving pertuzumab in addition to trastuzumab [ 70 ].
Pertuzumab has not been studied in pregnant women and, similarly to trastuzumab, is contraindicated during pregnancy [ 71 ]. There are no data regarding secretion of trastuzumab or pertuzumab in human milk or effects on the breastfed infant or milk production with trastuzumab in humans [ 72 ]; thus, it is not recommended. Experience with lapatinib during pregnancy is limited, and thus lapatinib cannot be recommended during pregnancy.
Becoming pregnant while taking tamoxifen or within 2 months after discontinuation has been associated with fetal malformations Goldenhar syndrome, manifested by oculoauriculovertebral dysplasia, as well as ambiguous genitalia , vaginal bleeding, and miscarriage [ 33 ], [ 75 ], [ 76 ], [ 77 ]. Given these reports, initiation of tamoxifen is recommended after delivery. Moreover, tamoxifen significantly delays postpartum milk production, and there are limited safety data regarding excretion of tamoxifen in human milk. Thus, we do not recommend tamoxifen during lactation [ 78 ]. Of note, the decision to delay endocrine treatment in order to allow lactation should be based on individual risk and include a balanced discussion of risk versus benefit.
Pregnancy is considered one of the few absolute contraindications to the use of radiotherapy RT because of the potential teratogenic and even lethal effects on the developing fetus. Most data regarding the effect of RT on pregnancy are based on animal models, although evidence in humans was also derived from the study of the atomic bombings of Hiroshima and Nagasaki, Japan [ 79 ]. The effects of RT on the developing fetus can be classified as lethal effects, malformations, and growth disturbances without malformations [ 80 ]. The two most important factors in discussing the effects of RT on the fetus are the actual dose received and the occurrence of the dose relative to the stage of pregnancy.
When one examines data from the atomic bombings in Japan, the most common effects seen in children whose mothers received incidental RT are microcephaly and mental retardation [ 81 ], [ 82 ], [ 83 ], [ 84 ]. Because RT is a known carcinogen, there is also concern for induction of malignancy in fetuses that are exposed. Although an issue of considerable debate, the exposure of a fetus in utero is postulated to increase the fetus's risk for cancer [ 85 ].
The malignancy with the most convincing link to RT is leukemia. From a pragmatic standpoint, we recommend against breastfeeding during RT treatment because the suckling effect from the infant can augment skin toxicity secondary to the RT, resulting in discomfort, skin breakdown, and possible infections i. BCDP is a major ethical and professional challenge for both the patient and the multidisciplinary treatment team. While the foundation of oncologic care is based on that of the NBCDP patient, there are many unique issues from the medical, surgical, and radiation oncology perspectives that must be considered to ensure safety to both the mother and developing fetus.
Many of these key points and important contraindications are summarized in Table 5. An informed discussion between the patient and her medical team that generates an individualized treatment plan, taking into account the timing of the pregnancy and the stage and subtype of the breast cancer, is essential to maximize benefit and minimize risk to the mother and fetus. Muss, Raeshell Sweeting, Carey K. Muss, Carey K. Carey K. The other authors indicated no financial relationships.
We dedicate this article to the memory of our beloved colleague and trusted surgeon, Dr. Keith Amos. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. This article was published online on 23 February An error was subsequently identified in the Author line. This notice is included in the online version to indicate that it has been corrected on 18 April User Name Password Sign In.
Zagar b , d , Aimee Faso e , Hyman B. Muss a , b , Raeshell Sweeting g and Carey K. Anders, M. Accepted August 18, Published online before print February 23, Materials and Methods. Implications for Practice. Previous Section Next Section. View this table: In this window In a new window. Table 1. Table 2. Suggested surgical management of breast cancer during pregnancy based on trimester at presentation. Table 3. Studies reporting on use and safety of chemotherapy during pregnancy. Table 4. Radiation Safety Issues Pregnancy is considered one of the few absolute contraindications to the use of radiotherapy RT because of the potential teratogenic and even lethal effects on the developing fetus.
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