PATHOPHYSIOLOGY AND CLINICAL ASSESSMENT

Staging and evaluation of pregnancy-associated breast cancer does not differ from staging and evaluation in the premenopausal woman with breast cancer. Yet, pregnant women often have more advanced disease because the significance of a breast mass is not often considered in the pregnant state and/or because of the endogenous hormone stimulation that occurs.4 The interpretation of normal physiologic changes that occur during and after pregnancy must be clearly separated from the persistence of masses in pregnant or lactating women. The potential risks of misdiagnosis or late diagnosis due to attributing masses in pregnant or lactating women as benign can lend itself to a missed diagnosis of pregnancyassociated breast cancer.4 The significant changes that ensue in the breast during pregnancy such as edema, hypervascularization, and lobular and glandular hyperplasia can make tumor detection challenging.5

Physical assessment Estrogen, progesterone, prolactin, and human placental lactogen are key hormones produced during pregnancy that play a role in breast growth.4 Hormonal and immunologic changes have not been proven to contribute to a favorable environment for the growth of breast cancer cells, but they are thought to mask the detection of early tumors in women.5,6,7 A comprehensive baseline breast examination should be performed in the early stages of pregnancy, before hormonal changes are extremely pronounced and obvious.5,7 Pregnancy-induced changes to a woman’s breast include a doubling in size and weight and increased blood flow and fat due to estrogen and progesterone, which in turn increases the size of the milk-producing glands; the areola increases in size and darkens; Montgomery tubercules (small nodules around the areola) produce a lubricant and cleanse the nipple; and the glandularity and density of breast tissue increases.5,7


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The baseline breast examination is critical to establishing any worrisome changes or differences that may be difficult to determine as the pregnancy progresses. A painless lump, thickening, or bloody discharge from the nipple are all manifestations of breast cancer.7 However, once the breast has become engorged, a bloody discharge from the nipple may be due to a benign condition related to breast changes during pregnancy. Any bloody discharge should be further evaluated for etiology.7

Clinical challenges with diagnosis One major contributor to the increased mortality in women with pregnancyassociated breast cancer is not related to the biology of these cancers, but the timing of diagnosis. Pregnancy-induced breast changes may be deceiving when assessing potentially abnormal changes in breast tissue. Late-stage diagnosis is not uncommon, and includes finding nodal involvement and distant metastases at the time of diagnosis. On average, diagnosis of pregnancy-associated breast cancer is delayed at least 5 to 7 months.6 Mammography has been associated with such delays given that the density of breast tissue during pregnancy can cause a very high number of false-negative findings in this population.5 A delay of 1 to 2 months increases the risk of metastasis to the axillary lymph nodes.5 In addition, worsened prognostic features are often appreciated in these women, such as higher grade, lower percentage of hormone receptor positivity, increased HER-2/neu overexpression, and higher Ki-67 nuclear antigen indices.6

With the challenges to diagnosis alone, independent of other high-risk factors, any concern of abnormal findings—either found on clinical examination or by patient report—should be immediately investigated. The risks associated with a lack of early diagnosis and intervention extend beyond the life of the woman, to that of the fetus. This complex diagnosis leaves very little room for independent decision-making. The multidisciplinary approach to managing breast cancer in the pregnant woman involves a collaboration between the oncologists, obstetrician, surgeon, nurse, radiation oncologist, pediatrician, and maternal-fetal medicine physician to provide care that encompasses the patient, her family, and the unborn child.5 If key disciplines are not at the forefront of the patient’s care, the outcomes for these women and their unborn fetus can be life threatening.

DIAGNOSIS IN THE PREGNANT WOMAN

Treatment goals for pregnancy-associated breast cancer are aimed at pregnancy preservation, establishing a personalized treatment plan based on disease stage, biologic features, and appropriate treatment modalities with careful consideration of the potential risks to the developing fetus.3,5 The focus of care is the same approach as that for nonpregnant women with a diagnosis of breast cancer. Triple assessments consist of a thorough physical examination, assessing for lumps and regional lymph nodes; mammography or ultrasound to determine whether the lump is cystic or solid (ultrasound is preferred due to the density of breast tissue in pregnancy); and a fine needle aspiration or core biopsy to determine the type of cancer.7

Diagnostic imaging Selecting the most sensitive and specific diagnostic tool that will lead to an accurate diagnosis without hindrance or delay in treatment is imperative. Opinions vary on which diagnostic imaging tool is the most exact and concrete for diagnosing pregnancy-associated breast cancer. The validity of mammography during pregnancy has been questioned; however, the specificity by which mammograms can detect and establish important information about microcalcifications, masses, or multicentric disease is established, and these imaging tests can be safely performed during pregnancy with proper abdominal shielding. Ultrasound images can be obtained safely during pregnancy, and are rapid and accurate. Magnetic resonance imaging (MRI) and computed tomography (CT), however, are contraindicated during pregnancy due to the risk of radiation exposure to the fetus.5