Jennifer E. Joh
Marie Catherine Lee
Presentation
A 28-year-old female, with a history of type I diabetes mellitus, presents to her obstetrician for an initial prenatal evaluation. Her last menstrual period was approximately 12 weeks prior to this visit. The patient has had two prior pregnancies requiring cesarean delivery. She states that she has developed a palpable breast mass over the past 7 months. The mass has grown substantially over the past month. She underwent mammography and focused ultrasound a month after first noticing the mass. The imaging at that time was negative for suspicious lesions, and no further evaluation was initiated.
Differential Diagnosis
The differential diagnosis of a breast mass in young women includes many benign entities such as fibroadenoma, lipoma, phyllodes tumor, fat necrosis, fibrocystic disease, galactocele, cyst, abscess, or accessory breast tissue. Surgical excision is recommended for phyllodes tumors and fibroadenomas that are symptomatic or enlarging. Fat necrosis is usually a posttraumatic or postoperative finding. Galactoceles generally develop months after discontinuation of lactation. Breast abscesses are usually associated with skin erythema, induration, and/or fever. During pregnancy, accessory breast tissue may swell and present as an enlarging mass in the axillary tail or in the axilla. Breast cancer is an uncommon diagnosis in this age group, with only 0.3% of all breast cancers occurring in women between the ages of 20 to 29.
Presentation Continued
The patient has no prior history of breast masses or breast biopsies. She notes a history of mastitis with a prior pregnancy. She has had no prior surgery other than the two cesarean sections. She had one maternal grandmother diagnosed with breast cancer but denies any additional family history of cancer, including breast or ovarian cancer. On review of systems, she denies trauma to the breast, skin changes, nipple retraction, or nipple discharge. Breast examination reveals a mass in the upper outer quadrant. There is also ipsilateral palpable axillary adenopathy. The contralateral breast is unremarkable.
Workup
Focused imaging in the form of mammography and ultrasound are the initial diagnostic tests after a thorough physical examination. With appropriate abdominal shielding, mammography is considered safe in pregnancy. Digital mammography is the preferred modality in premenopausal patients or those with dense breasts. Breast density may be increased by both lactational changes and premenopausal status (Figure 1). Masses, calcifications, and architectural distortion may all be visualized on mammography, despite the increased density of breast tissue seen during pregnancy and lactation. Focused ultrasound is used in conjunction with mammography for palpable breast masses to aid in the detection of solid versus cystic pathology. Sonography is more sensitive than mammography in the detection of breast cancer in pregnancy. In high-volume centers, ultrasound of the axilla may also help to detect the presence of axillary metastases. Evidence of axillary disease at initial diagnosis significantly affects recommendations for chemotherapy, surgery, and radiation therapy in patients with invasive breast cancer (Figure 2). Fetal effects of gadolinium-enhanced breast magnetic resonance imaging during pregnancy are unclear. Considering the prone position and the concerns regarding fetal exposure to gadolinium, breast magnetic resonance imaging is not considered a safe modality in pregnant patients.
FIGURE 1 • Digital mammography of a lactating patient with a high-density, lobular mass in the left breast (large arrow) and multiple enlarged lymph nodes in the axilla (small arrow)
FIGURE 2 • Axillary ultrasound demonstrates a lymph node with metastatic disease. There is complete loss of normal nodal architecture.
The current recommended modality for diagnosis of a breast mass is via image-guided, percutaneous biopsy with clip placement. Sonographically abnormal axillary lymph nodes should also undergo ultrasound-guided fine needle aspiration or core needle biopsy. In the case of a discordant breast biopsy result, surgical excision should be considered. Surgical excision in lieu of percutaneous biopsy is a feasible option but is outside the current recommended standard of care for initial tissue evaluation of a palpable breast mass. Furthermore, in the interest of minimizing risk to the pregnant patient as well as the fetus, avoidance of an additional surgical procedure is preferred.
Presentation Continued
In the 15th week of pregnancy, the patient had a focused breast ultrasound of the palpable mass. This demonstrated a 2.8-cm mass suspicious for malignancy. Ultrasound-guided core biopsy revealed invasive ductal carcinoma that was estrogen and progesterone receptor negative and HER2 negative. Ipsilateral axillary ultrasound also showed several abnormal lymph nodes; fine needle aspiration diagnosed metastatic disease on cytology. Both chest radiograph and ultrasound of the liver were negative for suspicious lesions.
Diagnosis and Treatment
Further evaluation and treatment of benign breast findings may be deferred until the postpartum period; however, a diagnosis of breast cancer during pregnancy warrants immediate attention. Invasive breast cancer is treated with multimodal therapy and may include surgery, chemotherapy, or radiation. For the pregnant patient, the timing and order of treatment is determined in part by gestational age as well as the stage of the cancer at diagnosis. Termination of the pregnancy does not improve outcome and should not be recommended to patients in the context of survival from breast cancer. Patients may maintain their pregnancy and safely undergo both local and systemic cancer treatment. Early delivery may be considered if felt to affect maternal oncologic outcome.
Pregnant patients with an invasive breast cancer diagnosis, particularly those with biopsy-proven axillary disease, should also have staging studies performed, in the form of chest radiograph and an ultrasound of the liver. Other imaging studies, such as computed tomography, bone, or positron emission tomography scans, should be deferred until the postpartum period. Any lesion suspicious for distant metastatic disease warrant a percutaneous biopsy, as patients with distant metastatic disease are not considered surgical candidates and should be initially treated with systemic chemotherapy.
Surgical Approach
For patients without evidence of distant disease, the goal is optimal curative treatment of the carcinoma without harm to the fetus; therefore, knowledge of all the treatment possibilities is important in deciding both the timing and type of operative procedure. Systemic chemotherapy may be administered in the second and third trimesters of pregnancy safely. However, adjuvant radiation therapy is contraindicated in all trimesters of pregnancy due to the risk of teratogenesis. Patients who have surgically resectable disease and are clinically node negative at presentation are not candidates for neoadjuvant chemotherapy, and should be advised to proceed to primary surgery for accurate staging. An outline of the decision-making process is illustrated in Figure 3.
FIGURE 3 • Surgical decision-making tree for pregnant patients diagnosed with breast cancer. BCS, breast-conserving surgery; MRM, modified radical mastectomy; ALND, axillary lymph node dissection; CTX, chemotherapy; XRT, radiation therapy; TM, total mastectomy; Tc-99, technetium-99; SLN, sentinel lymph node.
Key Considerations in Surgical and Treatment Decision Making:
1. Gestational age and associated surgical risk
2. Extent of breast and axillary disease
3. Need for and timing of systemic chemotherapy
4. Need for and timing of adjuvant radiation therapy
The second trimester is considered the optimum time period for surgery; organogenesis is complete, and the risk of preterm labor is low. Patients who present in the first trimester may undergo surgery without waiting until the second trimester; however, the potential effects of medications on organogenesis and the unquantifiable risk of spontaneous abortion in the first trimester mean that the overall risks incurred by surgery are poorly delineated. A detailed discussion of the potential risks is imperative. Women who present in the third trimester are generally recommended to defer surgery until the postpartum period due to the risk of preterm labor. General anesthesia is safe in pregnancy; however, local anesthesia or a paravertebral or a regional block is a safe alternative in all trimesters.
The extent of disease at presentation also plays a role in the decision for surgery. The traditional surgical choice for patients presenting with breast cancer during pregnancy is a modified radical mastectomy. However, breast conservation may be an option for patients presenting with limited in-breast disease in the third trimester or if chemotherapy is indicated and initiated during pregnancy. Decisions for breast-conserving surgery (BCS) require careful multidisciplinary planning due to the contraindications for radiation in pregnancy. Although blue dye mapping with lymphazurin or methylene blue is contraindicated, technetium-99 sulfur colloid for sentinel lymph node (SLN) surgery is safe and feasible in the second and third trimesters of pregnancy. In patients who have evidence of axillary disease on percutaneous biopsy, the SLN procedure is bypassed in lieu of an axillary node dissection at the time of breast surgery.
Case Conclusion
The patient was seen by high-risk obstetrics and medical oncology; because of her node-positive disease, she was recommended to have systemic chemotherapy. Based on the patient’s gestational age at presentation, the decision to proceed with primary surgery was made. After several discussions with the patient, her family, and a multidisciplinary team of physicians, she underwent BCS and axillary lymph node dissection in her 18th week of pregnancy. Surgical pathology demonstrated a 2.4-cm invasive ductal carcinoma and 2 of 24 positive lymph nodes. Chemotherapy was initiated in the 20th week of pregnancy and then discontinued at week 32 for a scheduled cesarean section. The delivery was uncomplicated, and she proceeded to have whole-breast radiation following the completion of her systemic therapy. BRCA mutation testing performed postpartum was negative for a deleterious mutation.
Postoperative Management
Both tamoxifen and Herceptin (trastuzumab) are contraindicated in pregnancy but can be initiated safely in the postpartum period if indicated. All patients presenting with primary breast cancer before the age of 50 should be considered for genetic counseling and testing. BRCA1 and BRCA2 mutation carriers are advised to consider prophylactic bilateral oophorectomy and mastectomy due to their inherited risk of breast and ovarian carcinomas after completion of childbearing. In lieu of prophylactic surgery, increased annual screening with breast magnetic resonance imaging and pelvic ultrasound may also be considered for known mutation carriers. During follow-up, patients diagnosed with breast cancer at any age should have annual screening mammography of both breasts if mastectomy was not performed as long as they are in good health.
TAKE HOME POINTS
· A multidisciplinary approach is essential to caring for the pregnant patient with breast cancer.
· Mammography with abdominal shielding and focused ultrasound are the appropriate initial diagnostic tests.
· Axillary staging is important in multimodal planning of breast cancer treatment.
· Evaluate for distant metastatic disease with a chest radiograph and ultrasound of the liver.
· Surgery is safest for both mother and fetus during the second trimester.
· SLN mapping may be performed with technetium-99 only.
· Systemic chemotherapy may be given during second and third trimesters.
· Radiation therapy is contraindicated in all three trimesters but may be initiated in the postpartum period.
· Genetic testing should be discussed in any young woman (<50 years of age) diagnosed with breast cancer.
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