This feature examines the case of a patient with newly diagnosed breast cancer in the setting of a first-trimester pregnancy presenting to our multidisciplinary breast cancer clinic.
A 30-year-old female at 6 weeks’ gestation of a highly desired pregnancy presented to our multidisciplinary breast cancer clinic with a new diagnosis of invasive ductal carcinoma of the right breast. The patient had just become aware of her pregnant state when she noted a mass in her right breast on self-examination. She was evaluated with a diagnostic mammogram with proper shielding and an ultrasound, confirming a 1.4-cm solid mass corresponding to the palpable lesion (Figures 1 and 2). Ultrasound-guided core needle biopsy was obtained and revealed a grade 3/3 invasive ductal carcinoma, estrogen receptor (ER)-negative, progesterone(Drug information on progesterone) receptor (PR)-negative, and human epidermal growth factor receptor 2 (HER2)-negative. On physical exam, she showed changes to the breast tissue consistent with early pregnancy, a palpable mass at the biopsy site, and no axillary adenopathy or contralateral findings. The remainder of her examination was likewise benign.
The patient’s past medical history was remarkable for a recent pregnancy loss at 12 weeks’ gestation 2 months prior. Her family history was pertinent for a strong family history of deep venous thrombosis in two first-degree relatives, and a breast cancer type 2 susceptibility protein (BRCA2)-associated breast cancer in a paternal aunt. The patient had not been tested for the familial BRCA2 gene mutation prior to her breast cancer diagnosis.
After her 12 weeks’ pregnancy loss, the patient had undergone workup for a hypercoagulable state, which is summarized in Table 1. Testing showed a low protein S activity level on two separate occasions and the presence of a double heterozygote state for mutations in the methylene tetrahydrofolate reductace (MTHFR) gene. Her homocysteine level was below the lower limit of normal. The patient denied a personal history of deep venous thrombosis or arterial thrombosis and was not receiving systemic anticoagulation.
Diagnostic Testing in Pregnancy
Dr. Jennifer Diamond: Ultrasound is ideal in evaluating a breast mass during pregnancy as it poses no risk to the fetus and has a sensitivity for malignancy approaching 100%.[1-3] Mammography also poses little risk to the fetus and is considered to be a safe imaging technique in pregnancy if necessary. The dose of radiation to the fetus with a standard bilateral mammography using abdominal shielding has been estimated at 0.004 Gy of radiation, falling well below the threshold for malformation in the fetus of 0.05 Gy of radiation. The earlier in pregnancy, the lower the exposure to the fetus.
If a hypoechoic mass concerning for malignancy is seen on ultrasound in the setting of pregnancy, is mammography necessary?
Dr. Laura Hardesty: Mammography is recommended for several reasons in this scenario. Although it is known that cancer is present at the site of the palpable mass, evaluation of the remainder of the ipsilateral breast and of the contralateral breast for the presence of additional sites of malignancy is necessary. Mammography allows for a “whole breast” view that cannot be obtained by sonography. Even if screening sonography of the entirety of both breasts is performed, only small portions of the breasts are imaged at one time. The radiologist must mentally “synthesize” a summary view of the breasts. As a result, mammography may provide a more complete understanding of the three-dimensional location of the cancer within the breast, particularly if there is more than one mass suspicious for cancer.
In addition, mammography is markedly more sensitive than sonography for detecting small calcifications that may indicate malignancy extending beyond the size of the sonographically imaged tumor, often ductal carcinoma in situ (DCIS). The difference in tumor size detectable by mammography vs sonography may also be significant, thus affecting treatment decisions regarding lumpectomy vs mastectomy.
In general, the mammographic density of the breasts increases with pregnancy-induced breast changes. This decreases the sensitivity for detecting breast masses, but does not decrease the ability to detect cancer-associated calcifications. The increase in mammographic glandular density becomes more marked as the pregnancy progresses, and is unlikely to be a limiting factor at 6 weeks’gestation
Dr. Diamond: Is there a role for breast magnetic resonance imaging (MRI) in the evaluation of the pregnant patient with newly diagnosed breast cancer?
Dr. Hardesty: The short answer is no. Unenhanced MRI of the breast could be performed during pregnancy; however, it is not useful for the evaluation of breast cancer. Intravenous gadolinium is contraindicated at any time during pregnancy, as it is known to cross the placenta and causes fetal abnormalities in animal models.[5,6]
Dr. Diamond: Radiographic staging exams are recommended in newly diagnosed stage IIB or higher cases or in the setting of concerning symptoms, physical exam findings, or laboratory abnormalities. What studies can safely be performed in pregnancy?
Dr. Hardesty: Sonography of the axilla is useful in screening for metastatic axillary lymphadenopathy, with subsequent ultrasound-guided core biopsy of suspicious axillary lymph nodes. Chest radiography can be performed with abdominal/pelvic lead apron shielding of the pregnancy. Sonography of the liver and/or MRI of the spine without gadolinium could also be performed at no risk to the fetus if clinically indicated.
Dr. Virginia Borges: In this patient who has a clinical T1, N0 tumor, I would recommend no alteration from the usual guidelines: checking hepatic function, a complete blood count with differential, and a chest x-ray with proper shielding for preoperative staging. A chest x-ray is recommended by National Comprehensive Cancer Network (NCCN) guidelines for staging of all newly diagnosed breast cancer, though published rates of actual detection of metastasis are between 0.93% and 1.2%.[7,8] If hepatic function is abnormal, then a liver ultrasound would also be recommended.
Surgical Management of Breast Cancer in Pregnancy
Dr. Diamond: How does a first-trimester pregnancy affect your surgical decision-making?
Dr. Christina Finlayson: Approximately 1% to 2% of pregnant women require a nonobstetric surgery during their pregnancy. Extensive experience has demonstrated that anesthesia at all stages of pregnancy is safe for both the mother and the fetus. Therefore, surgical therapy decisions for pregnancy-associated breast cancer can be made based on the oncologic situation, without the need for modification based on anesthetic concerns.
Sentinel lymph node sampling during pregnancy, however, is a controversial topic. Isosulfan blue dye and methylene blue dye are vital dyes and pregnancy category C drugs, while radiocolloid poses a radiation risk to the fetus. It is accepted that the vital blue dyes should not be used during pregnancy for sentinel lymph node localization, but the use of radiocolloid during pregnancy has been reported in the literature with modeling in nonpregnant women estimating the radiation dose to the fetus to be below the threshold for malformation.[10,11] A very small series of patients given a radioactive tracer showed successful localization of the sentinel lymph node without adverse fetal outcome. From the currently available literature, localization of the sentinel lymph nodes with radioactive tracer alone appears to be a safe procedure. For mothers who do not want to assume the theoretical risk of early radiation exposure to the fetus, an axillary node dissection continues to be an excellent and appropriate technique for staging the axilla.
Dr. Diamond: The family history of BRCA2-associated breast cancer and young age at diagnosis make a genetic cancer syndrome likely in this patient. Would the presence of a BRCA2 mutation change your surgical recommendations for this patient?
Dr. Finlayson: Patients with a known BRCA1 or BRCA2 mutation have similar outcomes with local therapy as patients without a known gene defect. However, they have a much higher risk of subsequent cancers than patients without a genetic predisposition. The risk of a second cancer in the contralateral breast within the next 10 years can be as high as 40% to 50% in some series.[13-15] Therefore, many women select mastectomy to treat their known cancer, and contralateral prophylactic mastectomy for maximal risk reduction against a second breast cancer.
In an international cohort of BRCA1/2 gene mutation carriers with breast cancer, the rate of contralateral prophylactic mastectomy was 27% overall, and 49% in North American women. In this cohort, women choosing contralateral prophylactic mastectomy were younger at the time their cancer was diagnosed, and more likely to undergo ipsilateral mastectomy for the treatment of their known cancer.
In this young woman with a family history of a BRCA2 gene mutation, the decision for breast conservation vs mastectomy to treat her known breast cancer will likely be influenced by the results of her genetic testing. In this situation, lumpectomy and nodal sampling can be performed followed by initiation of systemic therapy as appropriate while her genetic testing is being performed. Radiation therapy, however, should not be initiated until after the genetic testing results are available, and the patient has decided to forgo mastectomy due to either personal choice or negative gene mutation results.
Postlumpectomy whole-breast irradiation followed by mastectomy should be avoided, as it subjects patients to unnecessary treatment, is redundant, and can complicate potential reconstructive options. Prosthetic reconstruction in the setting of radiation therapy to the breast or chest wall is associated with an increase in complications including capsular contracture and infection.[17,18] Autologous reconstruction after radiation therapy can also lead to decreased aesthetic outcomes and increased contracture rates.