Published online before print February 16, 2006, 10.1148/radiol.2391050083
(Radiology 2006;239:52-60.)
© RSNA, 2006
Imaging of Breast Cancer Diagnosed and Treated with Chemotherapy during Pregnancy1
Wei Tse Yang, MD,
Mark J. Dryden, MD,
Karin Gwyn, MD,
Gary J. Whitman, MD and
Richard Theriault, MD
1 From the Departments of Diagnostic Radiology (W.T.Y., M.J.D., G.J.W.) and Breast Medical Oncology (K.G., R.T.), University of Texas, M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Unit 57, Houston, TX 77030. Received January 18, 2005; revision requested March 22; revision received April 20; accepted June 1.
Address correspondence to W.T.Y. (e-mail: wyang{at}di.mdacc.tmc.edu).
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ABSTRACT
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Purpose: To retrospectively assess mammography, high-frequency-transducer ultrasonography (US), and color Doppler US for the initial and subsequent evaluation of breast cancer diagnosed and treated with chemotherapy during pregnancy.
Materials and Methods: A retrospective study of clinical records between January 1989 and December 2003 of women with breast cancer diagnosed and treated with chemotherapy during pregnancy was performed after waiver of informed consent was obtained. The study was approved by an institutional review board and was HIPAA compliant. Mammograms and sonograms were reviewed by two mammographers using the Breast Imaging Reporting and Data System (BI-RADS) mammographic and US lexicon. US assessment of the regional lymph node basins, including the axillary, infraclavicular, internal mammary, and supraclavicular regions, was documented. US was used to evaluate response to therapy in the breast and the regional lymph nodes in women who underwent neoadjuvant chemotherapy.
Results: Twenty-three women with 24 cancers that were imaged prior to surgery with mammography (n = 3), US (n = 4), or mammography and US (n = 17) were included in the study. The histologic diagnosis of the primary tumor was invasive ductal cancer in 22 lesions, and the diagnosis was invasive carcinoma in the two other cancers. The median age in this study was 34 years (range, 24–45 years). Of the 20 women who underwent preoperative mammography, findings were positive for malignancy in 18 of 20 (90%) cancers despite dense breast parenchymal patterns (BI-RADS types 3 and 4). A mass in all 21 cancers (100%) was depicted in the 20 women who underwent breast and nodal US. US correctly depicted axillary metastasis in 15 of 18 women who underwent US nodal assessment. Of the 12 patients who were evaluated for response to chemotherapy, US demonstrated complete response in two patients, partial response in three, stable findings in one, and progression of disease in six.
Conclusion: Breast cancer diagnosed during pregnancy is mammographically evident despite dense parenchymal background. US, when performed, demonstrates all masses and provides information regarding response to neoadjuvant chemotherapy.
© RSNA, 2006
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INTRODUCTION
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Pregnancy-associated breast cancer is defined as breast cancer that occurs during pregnancy or within 1 year of delivery. Its incidence is estimated at one in 3000 to one in 10 000 pregnancies (1,2). Cancer diagnosed during lactation is considered likely to have been present during pregnancy and therefore is equivalent in biologic characteristics and outcome to cancer diagnosed during pregnancy. Physiologic changes that are unique to pregnancy and lactation and that occur in response to the increased hormone levels associated with pregnancy and lactation result in an increase in breast volume and firmness. These changes may make clinical and radiologic detection and evaluation of breast masses difficult during pregnancy and lactation.
The goals of breast cancer treatment in a pregnant patient are the same as the goals of treatment in a nonpregnant patient: local control of disease and prevention of systemic metastases. Although local and systemic treatment strategies for a pregnant patient with breast cancer are similar to those for a nonpregnant patient, some modifications may be necessary in pregnant patients to minimize fetal harm. For example, breast irradiation, chest wall irradiation, or both are postponed until after delivery because of risks of fetal exposure to radiation.
Because pregnant breast cancer patients have more locally advanced breast cancer at presentation than do nonpregnant patients, neoadjuvant or primary systemic (neoadjuvant) chemotherapy may be appropriate during pregnancy (7–12). The majority of information regarding the safety of chemotherapy in pregnant breast cancer patients is derived from retrospective case series and case-control studies. However, there is a report—by Berry et al (13)—on a prospective cohort of pregnant breast cancer patients who were treated with systemic chemotherapy while pregnant. Berry et al concluded that pregnant breast cancer patients could be treated with 5-fluorouracil, doxorubicin hydrochloride, and cyclophosphamide during the second and third trimesters with minimal harm to the fetus (13). Currently, there are few data to support the safety of non–anthracycline-based combination chemotherapy or hormonal therapy during pregnancy (14).
The assessment of the effectiveness of mammography and ultrasonography (US) in pregnant breast cancer patients has been limited because there are few published studies (3–6). In most of these studies, the majority of patients had pregnancy-associated breast cancer and were not actually pregnant when the mammograms, US scans, or both were obtained. Cancer diagnosed during lactation may reflect a lack of awareness by both the patient and physician of masses that may have been present during pregnancy. A lack of awareness results in potential delays in diagnosis and treatment of up to 19 months.
The purpose of our study was to retrospectively assess mammography, high-frequency transducer sonography, and color Doppler sonography for the initial and subsequent evaluation of breast cancer diagnosed and treated with chemotherapy during pregnancy.
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MATERIALS AND METHODS
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We retrospectively reviewed the clinical records at our institution of all pregnant women with breast cancer diagnosed and treated with an institutional review board–approved clinical protocol from January 1989 to December 2003. All patients were treated with anthracycline-based chemotherapy. A waiver of informed consent was obtained from the institutional review board that approved our study. Our study was Health Insurance Portability and Accountability Act (HIPAA) compliant.
Clinical Information
The clinical charts were reviewed by one author (K.G.) to collect information on the pathologic characteristics of the breast tumors, including histologic characteristics, estrogen and progesterone receptor status, and HER-2/neu status. The clinical and pathologic tumor stages were determined by using the American Joint Committee on Cancer (AJCC) cancer staging system (15). The number of cycles of chemotherapy given while the patient was pregnant was recorded, as were the number of cycles and the type of chemotherapy for those women who received neoadjuvant chemotherapy. Vital status was determined by reviewing the Social Security Death Index for those women with a Social Security number (n = 22) and the medical record for a patient's status at her last clinic visit. The majority of this information was collected before implementation of HIPAA guidelines. With implementation of HIPAA, the protocol was made HIPAA compliant per institutional guidelines as required. Length of follow-up (in months) was the interval from a patient's first clinic visit at our institution to the patient's last contact with our institution.
Imaging
Mammography was performed with one of two types of units (Lorad M3, Hologic, Boston, Mass; DMR series, GE Healthcare, Milwaukee, Wis). Standard three-view diagnostic mammographic examinations were performed, and additional views were obtained as deemed necessary. Two mammographers (M.J.D., W.T.Y.)—one with 6 years and one with 9 years of experience in breast imaging, respectively—reviewed all available mammograms and sonograms. Agreement on the presence (or absence) of findings was by consensus. Breast parenchymal density was classified according to the American College of Radiology Breast Imaging Reporting and Data System (BI-RADS) (16). Mammograms were reviewed to determine the presence of focal masses, calcifications, asymmetric density, architectural distortion, and associated features, such as skin thickening and retraction, nipple retraction, and axillary lymphadenopathy.
Real-time gray-scale and color Doppler sonography (Elegra; Siemens Medical, Erlangen, Germany) was performed by the attending radiologist assigned to breast US in the institution. This group comprised 10 radiologists, including three authors (M.J.D., W.T.Y., G.J.W.). Sonograms were assessed (M.J.D., W.T.Y.) for the presence of masses (solid or cystic) and their shape, margins, echo pattern, and posterior acoustic features; presence of calcifications; vascularity determined at color Doppler imaging; and effects on surrounding tissue, according to the BI-RADS US lexicon (16,17). Disease was also assessed as unifocal, multifocal, or multicentric in all patients who underwent sonography. Sonographic assessment of the regional lymph node basins, including the axillary, infraclavicular, internal mammary, and supraclavicular regions, was documented according to previously published criteria (18,19).
US Evaluation of Response to Therapy
Disease sites in the breast and the regional lymph nodes were assessed during each sonographic examination to evaluate for response to therapy. On average, two US examinations were performed in each woman (range, one to four examinations) over a period of 5 months (range, 2–10 months). Assessment of tumor response was classified by using standard criteria of the World Health Organization as (a) complete response if there was complete resolution of all masses and abnormalities, (b) partial response if there was at least a 50% reduction in the product of the bidimensional tumor measurements, (c) stable disease if there was a less than 50% reduction or less than 25% increase in the product of the bidimensional tumor measurements, and (d) progressive disease if there was at least a 25% increase in the product of the bidimensional tumor measurements.
Pathologic Evaluation at Surgery
In all women who underwent surgery, had pathologic evaluation was performed to document the extent of residual tumor and axillary nodal status.
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RESULTS
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Clinical Information
Fifty-two women with a diagnosis of breast cancer were treated with chemotherapy during pregnancy; images were available for review for 23 of the women. These 23 women, who had 24 cancers imaged with mammography alone (n = 3), sonography alone (n = 4), or both mammography and sonography (n = 17), were included in the study cohort. Multiple malignant lesions within a single breast were defined as a single cancer with multifocal or multicentric distribution, while bilateral breast cancer was defined as two cancers in this study.
The median age was 34 years (range, 24–45 years). Only three women had a first-degree family history of breast or ovarian cancer. With regard to self-reported ethnicity, 15 of 23 (65%) were Caucasian, four (17%) were African American, and four (17%) were Hispanic. Most women (n = 17) presented with a palpable mass. Breast swelling (n = 3) and breast erythema (n = 2) were less common at presentation. One woman in whom cancer was diagnosed at mammographic screening discovered she was 7 weeks pregnant 1 week later. The median follow-up for the 23 women in this cohort is almost 57 months (range, 14–173 months). As of March 31, 2005, 14 women (61%) were alive and nine had died (eight died of breast cancer and one died of a pulmonary embolism after a cesarean delivery).
Clinical stage was unknown in three women in whom nodal status was unknown. Of the other 20 women, on the basis of the AJCC staging system 12 (60%) had stage III breast cancer and six (30%) had stage II breast cancer. Only one of the 20 (5%) women had clinical stage I breast cancer. One patient had locally advanced breast cancer metastatic to the liver (stage IV). The clinical tumor stage for the disease in the 23 women is as follows: eight (35%) women had T4 tumors, four (17%) had T3 tumors, eight (35%) had T2 tumors, and three (13%) had T1 tumors. Nodal status was unknown in three of 23 women who underwent surgery before being seen at our institution, and clinical nodal status was therefore not available. Of the other 20 women, 16 had node-positive breast cancer (clinical and fine-needle aspiration biopsies proved): N1 in nine (45%) and N2 in seven (35%). Only four (20%) of the women had clinical node-negative findings.
Eighteen patients had invasive ductal carcinoma, and two patients had what was described as invasive carcinoma. One patient had a ductal carcinoma in one breast and a malignant phyllodes tumor in the other breast. Two patients had a diagnosis of inflammatory breast cancer. Fifteen of 24 (63%) tumors were poorly differentiated, four (17%) were moderately differentiated, and four (17%) were not reviewed for nuclear grade. Of the 15 tumors that had tissue for review, 11 (73%) had estrogen-receptor–negative findings, four (27%) had estrogen-receptor–positive findings; and 13 (87%) had progesterone-receptor–negative findings, and two (13%) had progesterone-receptor–positive findings. Of the 14 tumors with HER-2/neu status reviewed, nine (64%) had HER-2/neu negative findings, and five (36%) had HER-2/neu positive findings at immunohistochemistry, fluorescence in situ hybridization, or both.
Imaging Results
Three patients did not undergo preoperative mammography. Mammographic findings were positive for malignancy in 18 of the 20 (90%) women who had undergone preoperative mammography, despite dense breast parenchymal patterns (BI-RADS type 3, n = 14; BI-RADS type 4, n = 4). The mammographic findings included a mass (n = 7), a mass and calcifications (n = 2), suspicious calcifications (n = 4) (Fig 1), calcifications and increased breast density (n = 2), focal asymmetric breast density (n = 1) (Fig 2), architectural distortion (n = 1), and diffusely increased breast density (n = 1). Six patients had skin and trabecular thickening, and six patients had axillary lymphadenopathy (Fig 2).
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Figure 1a: Palpable mass at 24 weeks gestation in a 32-year-old woman. (a) Magnification view mammogram of left breast in craniocaudal projection shows extensive pleomorphic microcalcifications (arrows). (b) Corresponding longitudinal US image shows irregular solid hypoechoic mass (long arrows) with internal calcifications (short arrows) corresponding to mammographic finding.
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Figure 1b: Palpable mass at 24 weeks gestation in a 32-year-old woman. (a) Magnification view mammogram of left breast in craniocaudal projection shows extensive pleomorphic microcalcifications (arrows). (b) Corresponding longitudinal US image shows irregular solid hypoechoic mass (long arrows) with internal calcifications (short arrows) corresponding to mammographic finding.
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Figure 2a: Palpable mass at 22 weeks gestation in a 36-year-old woman. (a) Spot compression mammogram in craniocaudal projection shows focal asymmetric density (arrows) in lateral left breast. (b) Transverse US scan shows solid irregular hypoechoic mass (arrows) with indistinct margins. (c) Mediolateral oblique left mammogram shows high-density left axillary nodes (arrows). (d) Transverse US scan in left axillary region shows enlarged hypoechoic lymph node (arrows) shown to be metastasis with US-guided fine-needle aspiration biopsy results.
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Figure 2b: Palpable mass at 22 weeks gestation in a 36-year-old woman. (a) Spot compression mammogram in craniocaudal projection shows focal asymmetric density (arrows) in lateral left breast. (b) Transverse US scan shows solid irregular hypoechoic mass (arrows) with indistinct margins. (c) Mediolateral oblique left mammogram shows high-density left axillary nodes (arrows). (d) Transverse US scan in left axillary region shows enlarged hypoechoic lymph node (arrows) shown to be metastasis with US-guided fine-needle aspiration biopsy results.
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Figure 2c: Palpable mass at 22 weeks gestation in a 36-year-old woman. (a) Spot compression mammogram in craniocaudal projection shows focal asymmetric density (arrows) in lateral left breast. (b) Transverse US scan shows solid irregular hypoechoic mass (arrows) with indistinct margins. (c) Mediolateral oblique left mammogram shows high-density left axillary nodes (arrows). (d) Transverse US scan in left axillary region shows enlarged hypoechoic lymph node (arrows) shown to be metastasis with US-guided fine-needle aspiration biopsy results.
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Figure 2d: Palpable mass at 22 weeks gestation in a 36-year-old woman. (a) Spot compression mammogram in craniocaudal projection shows focal asymmetric density (arrows) in lateral left breast. (b) Transverse US scan shows solid irregular hypoechoic mass (arrows) with indistinct margins. (c) Mediolateral oblique left mammogram shows high-density left axillary nodes (arrows). (d) Transverse US scan in left axillary region shows enlarged hypoechoic lymph node (arrows) shown to be metastasis with US-guided fine-needle aspiration biopsy results.
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Three patients did not undergo preoperative sonography. Sonographic findings were positive for all 21 malignancies in all 20 women who underwent breast and nodal basin sonography. A breast mass was identified in all 21 cancers diagnosed in 20 women (Figs 1–3). The most frequent sonographic features of these masses were hypoechogenicity (n = 21), indistinct margins (n = 17), irregular shape (n = 12), increased vascularity at color Doppler sonography (n = 11), no posterior acoustic phenomenon (n = 10), skin and subcutaneous edema (n = 4), and calcifications within a mass (n = 2). One woman had bilateral breast disease, and five women had more than one lesion; four were multicentric (Fig 3), and one was multifocal at sonography.
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Figure 3a: Palpable mass at 20 weeks gestation in a 33-year-old woman. (a) Bilateral craniocaudal mammograms show no abnormality despite palpable mass (skin marker) in right breast. (b) Sonogram with extended–field-of-view imaging shows index palpable lesion as irregular mass with indistinct margins (short arrow) and as associated with mass in separate quadrant (long arrow), which confirms multicentric disease. (c) Transverse US scan shows three separate nonpalpable solid nodules with indistinct margins (arrows), consistent with multifocal disease. (d) Transverse power Doppler US in infraclavicular region shows oval, homogeneously hypoechoic node (arrows) deep to pectoralis major ( ) and pectoralis minor (+) muscles. Adjacent vessel is yellow-orange.
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Figure 3b: Palpable mass at 20 weeks gestation in a 33-year-old woman. (a) Bilateral craniocaudal mammograms show no abnormality despite palpable mass (skin marker) in right breast. (b) Sonogram with extended–field-of-view imaging shows index palpable lesion as irregular mass with indistinct margins (short arrow) and as associated with mass in separate quadrant (long arrow), which confirms multicentric disease. (c) Transverse US scan shows three separate nonpalpable solid nodules with indistinct margins (arrows), consistent with multifocal disease. (d) Transverse power Doppler US in infraclavicular region shows oval, homogeneously hypoechoic node (arrows) deep to pectoralis major () and pectoralis minor (+) muscles. Adjacent vessel is yellow-orange.
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Figure 3c: Palpable mass at 20 weeks gestation in a 33-year-old woman. (a) Bilateral craniocaudal mammograms show no abnormality despite palpable mass (skin marker) in right breast. (b) Sonogram with extended–field-of-view imaging shows index palpable lesion as irregular mass with indistinct margins (short arrow) and as associated with mass in separate quadrant (long arrow), which confirms multicentric disease. (c) Transverse US scan shows three separate nonpalpable solid nodules with indistinct margins (arrows), consistent with multifocal disease. (d) Transverse power Doppler US in infraclavicular region shows oval, homogeneously hypoechoic node (arrows) deep to pectoralis major () and pectoralis minor (+) muscles. Adjacent vessel is yellow-orange.
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Figure 3d: Palpable mass at 20 weeks gestation in a 33-year-old woman. (a) Bilateral craniocaudal mammograms show no abnormality despite palpable mass (skin marker) in right breast. (b) Sonogram with extended–field-of-view imaging shows index palpable lesion as irregular mass with indistinct margins (short arrow) and as associated with mass in separate quadrant (long arrow), which confirms multicentric disease. (c) Transverse US scan shows three separate nonpalpable solid nodules with indistinct margins (arrows), consistent with multifocal disease. (d) Transverse power Doppler US in infraclavicular region shows oval, homogeneously hypoechoic node (arrows) deep to pectoralis major () and pectoralis minor (+) muscles. Adjacent vessel is yellow-orange.
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Two patients underwent imaging at an outside institution, and axillary nodal assessment was not performed. Sonography correctly depicted axillary metastasis in 15 of 18 (83%) women who underwent sonographic nodal assessment. Two of three women who were node negative at sonography did not reveal axillary nodal metastasis at surgery; the third woman did not have pathologic information available for review. Sonography demonstrated clinically occult infraclavicular (Fig 3), supraclavicular, or internal mammary nodal disease in seven patients. Cancer was depicted with US-guided fine-needle aspiration biopsy at diagnosis, and disease in these women was upstaged to N3 according to the AJCC staging criteria (15).
There were two false-negative mammograms; one was in a 33-year-old woman (BI-RADS type 3 parenchymal patterns) and one was in a 34-year-old woman (BI-RADS type 4 parenchymal patterns), both of whom had dense breasts. Sonography depicted a 3.0-cm breast mass in the 33-year-old woman (Fig 3) and a 1.6-cm breast mass in the 34-year-old woman.
US Evaluation of Response to Therapy
Because of the advanced clinical tumor stage at patient presentation, 16 of 23 (70%) pregnant patients in this series underwent neoadjuvant chemotherapy in an attempt to downstage the tumors prior to surgery. The Table depicts the clinical and pathologic stage of disease in the women treated with neoadjuvant chemotherapy while pregnant, as well as the number and types of chemotherapy and the surgery performed (if the tumor was surgically resectable). Sixteen women underwent anthracycline-based neoadjuvant chemotherapy while pregnant and additional non–anthracycline-based chemotherapy after delivery. Twelve of these 16 women underwent sonographic evaluation of tumor response to chemotherapy. Sonography of the index breast tumor demonstrated a complete response in two women, a partial response in three (Fig 4), stable findings in one, and progression of disease in six. Five patients whose disease progressed during chemotherapy were given different chemotherapeutic agents after delivery, and one patient received radiation therapy while pregnant, as she was not a surgical candidate. Of the five women with multicentric or multifocal disease who underwent neoadjuvant chemotherapy, three responded to therapy and subsequently underwent mastectomy as standard of care, and two with disease that progressed during chemotherapy did not undergo surgery. Assessment of axillary nodal disease demonstrated partial response in three women, stable disease in three, progressive disease in five, and no nodal disease in one.
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Figure 4a: Palpable mass in left upper outer quadrant at 30 weeks gestation in a 34-year-old woman. (a) Bilateral mediolateral oblique mammograms show focal asymmetric density (arrow) in left breast that corresponds to palpable finding. This was not visible on craniocaudal projection (not shown). (b) Transverse US scan of left breast shows solid lobular mass (arrows) with indistinct margins and posterior acoustic enhancement (arrowheads). (c) Evaluation of response to neoadjuvant chemotherapy by using US 7 weeks later shows reduction in size of tumor (arrows) in left breast.
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Figure 4b: Palpable mass in left upper outer quadrant at 30 weeks gestation in a 34-year-old woman. (a) Bilateral mediolateral oblique mammograms show focal asymmetric density (arrow) in left breast that corresponds to palpable finding. This was not visible on craniocaudal projection (not shown). (b) Transverse US scan of left breast shows solid lobular mass (arrows) with indistinct margins and posterior acoustic enhancement (arrowheads). (c) Evaluation of response to neoadjuvant chemotherapy by using US 7 weeks later shows reduction in size of tumor (arrows) in left breast.
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Figure 4c: Palpable mass in left upper outer quadrant at 30 weeks gestation in a 34-year-old woman. (a) Bilateral mediolateral oblique mammograms show focal asymmetric density (arrow) in left breast that corresponds to palpable finding. This was not visible on craniocaudal projection (not shown). (b) Transverse US scan of left breast shows solid lobular mass (arrows) with indistinct margins and posterior acoustic enhancement (arrowheads). (c) Evaluation of response to neoadjuvant chemotherapy by using US 7 weeks later shows reduction in size of tumor (arrows) in left breast.
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Pathologic Findings at Final Surgery
Seven of 23 (30%) women whose disease progressed during chemotherapy were not surgical candidates. Pathologic examination of 16 (70%) women who were surgical candidates showed no residual disease in the breast in three and residual disease in 13. Twelve patients who had unifocal disease at sonography at diagnosis and who were ultimate surgical candidates showed unifocal disease at surgery. One patient with unifocal disease at diagnosis progressed while undergoing chemotherapy and had multifocal disease at surgery.
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DISCUSSION
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We found that breast cancer was mammographically visible in 90% of the pregnant women with invasive breast cancer. This percentage in our series may have been influenced by the fact that the majority of our patients had more advanced stage breast cancer. However, this percentage is consistent with previously published reports that noted that pregnant breast cancer patients usually have a more advanced stage disease at presentation (7–12), which may reflect delays in diagnosis (both patient and physician related) and the younger patient age at diagnosis.
Our findings regarding mammographic diagnosis of breast cancer during pregnancy concur with those of Liberman et al (3), as well as those of Ahn et al (6). An important difference between our study and those published previously is that in our study, all breast cancer cases were diagnosed, imaged, and treated during pregnancy, while most of the previously published studies included women with breast cancer diagnosed in the postpartum period (3–6). To our knowledge, ours is the largest reported series of pregnant breast cancer patients who have been imaged with mammography and US while pregnant.
An important finding from our study is that six of the 18 (33%) tumors that were mammographically visible exhibited secondary features of malignancy, such as increased breast density and architectural distortion. These secondary features can be subtle and may account for false-negative findings during interpretation of the images. The two women in whom no abnormality was visible at mammography, but in whom US revealed suspicious masses subsequently shown to be cancer with biopsy results, re-emphasize the complementary role of mammography and US in the diagnosis of breast cancer in the pregnant patient.
The US findings in our study are similar to the findings in the study on pregnancy-associated breast cancers previously reported by Liberman et al (3), which found that US demonstrated a mass in all six patients. The study by Ahn et al involved a series of 19 sonographically depicted pregnancy-associated breast cancers (6). Ahn et al found a complex echo pattern in 14 of the 19 cancers in their series and a marked cystic component in four of the 19 cancers (6). Cystic components were demonstrated in all three medullary cancers in their series (6). There were no medullary cancers in our series, and none of the sonographically visible cancers in our series showed a cystic component.
Our findings confirm the useful role of sonography in the evaluation of the breast in pregnant women. In the case of a palpable abnormality, sonography depicts whether the palpable area corresponds to a mass or to normal breast tissue. Also, sonography allows for characterization of the abnormality in order to evaluate the need for biopsy, according to previously published criteria (20). Sonography may lead to the diagnosis of additional tumors not imaged at mammography. In our series, sonography led to the diagnosis of multicentric cancers in four patients and enabled accurate regional staging of the cancers that facilitated the appropriate treatment plan. For example, sonography depicted axillary metastases that were confirmed at US guided fine-needle aspiration biopsy in 15 of the 18 women we scanned at initial breast cancer diagnosis.
Additionally we demonstrated that sonography can aid in the assessment of response of pregnant women to neoadjuvant chemotherapy. In this cohort, 12 of 23 pregnant women underwent serial sonography to monitor neoadjuvant chemotherapy response during pregnancy. Abnormal regional lymph nodes demonstrated at US served as an additional site of disease from which to monitor response to therapy. Axillary nodal response to therapy may be an important marker for prognosis, because nodal disease is thought to reflect the presence of occult disseminated disease.
Most cases of breast cancer were diagnosed in young women in this study. Young-age breast cancer is defined as cancer occurring in women aged 35 and younger. These cancers are usually detected as painless, palpable masses (21). Routine screening mammography is not performed in women of this age because their breasts are relatively dense, the probability of malignancy is low, and the risk of radiation-associated carcinogenesis may not be negligible. In addition, the usefulness of mammography in patients older than 40 years has been questioned (22–24). One reason for this is that false-negative mammographic examination findings may delay the diagnosis of breast cancer. Mammography in young nonpregnant and nonlactating women will reveal dense mammary parenchyma in 52%–78% of women (3,21). When mammography is used in pregnant women, common findings include an overall increase in breast size, diffusely increased parenchymal density, and a prominent ductal pattern—findings that correspond to the hormonally induced proliferative glandular changes that occur during pregnancy (3,21). These commonly observed findings in pregnancy might decrease the efficacy of mammography in young and pregnant women. However, our findings, together with those in previous studies, indicate that mammography is effective in the diagnosis of malignancy in pregnant women (3,6).
It is prudent to consider the risk-to-benefit ratio when contemplating mammography for women younger than 30 years. The radiation dose to the breast with current techniques is small: <1 rad (1 cGy) per examination (25). Adverse effects of fetal radiation exposure include congenital malformations, retardation of growth, perinatal death, and postnatal neoplasia. Although concrete data are sparse, some investigators believe that exposure to less than 2 rad (0.02 Gy) of radiation during gestation will not increase the incidence of fetal malformation (26). Most authorities believe that with proper abdominal shielding, mammography poses little risk of radiation exposure to the fetus, as the radiation dose to the fetus is estimated at less than 100 mrad (0.01 Gy) (27,28).
We believe that mammography and sonography have a complementary role in imaging the pregnant patient and suggest that sonography be used as the initial imaging modality in symptomatic pregnant women. The imaging indications for biopsy, which include the presence of complex cysts, solid masses, indeterminate calcifications, and persistent inflammatory changes, remain the same as for nonpregnant women. However, mammography remains useful in the diagnosis of breast cancer during pregnancy. It may demonstrate malignant calcifications not imaged at US, and thus we believe mammography should be performed on pregnant women with a diagnosis of invasive or in situ malignancy. Both breasts of the pregnant woman with a diagnosis of breast cancer should be imaged to rule out bilateral malignant disease.
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FOOTNOTES
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Abbreviations: AJCC = American Joint Committee on Cancer • BI-RADS = Breast Imaging Reporting and Data System
Author contributions: Guarantor of integrity of entire study, W.T.Y., K.G., R.T.; study concepts/study design or data acquisition or data analysis/interpretation, all authors; manuscript drafting or manuscript revision for important intellectual content, all authors; approval of final version of submitted manuscript, all authors; literature research, W.T.Y., K.G.; clinical studies, W.T.Y., M.J.D., K.G., R.T.; statistical analysis, W.T.Y., K.G.; and manuscript editing, all authors
Authors stated no financial relationship to disclose.
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ABSTRACT
INTRODUCTION
