Basics
Description
- Breast cancer in pregnancy is defined as breast cancer that is diagnosed during pregnancy, during lactation, and up to 12 months postpartum.
- Breast cancer is the most common malignancy in pregnancy with an estimated prevalence of 1 per 3,000 pregnancies (1).
Epidemiology
Incidence
- Gestational breast cancer is one of the most common pregnancy-associated malignancies, second only to cervical cancer.
- Breast cancer is found in about 1 in every 3,000 pregnant women (2,3).
Etiology and Pathophysiology
Genetics
- BRCA1 and BRCA2 mutation carriers have greatly increased risk of breast cancer overall and may be more likely to develop breast cancer during pregnancy (4).
- Multiparity appears protective in BRCA1 carriers but is associated with increased risk in BRCA2 carriers.
- Other significant mutations include p53 (Li-Fraumeni syndrome) and PTEN (Cowden syndrome) (5).
Risk Factors
- Age
- Increased risk with advanced age
- First pregnancy after age 30 years increases risk.
- Early menarche and late menopause
- Family history
- Breast cancer in 1st-degree relatives
- 1st-degree relatives with premenopausal breast cancer further increases risk.
- Nulliparity
- Exposure to radiation
General Prevention
- Reduce the risk of breast cancer by maintaining a healthy weight.
- The benefits with moderate exercise such as brisk walking are seen at all age groups including postmenopausal women (6).
Commonly Associated Conditions
- Women with gestational diabetes mellitus (GDM) are at one and a half times greater risk of breast cancer as compared with women who do not have GDM.
- Lower risk of breast cancer is observed in women who have pregnancy-related hypertensive disorders such as preeclampsia.
Diagnosis
History
- Most common symptom of breast cancer is a new lump or mass.
- Any mass in the breast during pregnancy must be investigated.
- Women may present with breast pain, nipple pain, or nipple discharge (other than breast milk).
- Inflammatory breast cancer present with erythema, edema, warmth, and tenderness.
Physical Exam
- Physiologic breast changes during pregnancy
- Engorgement, hypertrophy, make physical exam and interpretation of findings more difficult (3).
- Inspect and palpate both breasts with patient sitting up and supine; evaluate for axillary adenopathy.
Differential Diagnosis
- Breast cancer until proven otherwise
- Skin thickening-inflammatory carcinoma and mastitis
- Galactocele (milk retention cyst), abscess, fibroadenoma, lobular hyperplasia, lipoma, hamartoma, traumatic fat necrosis (3)
Diagnostic Tests & Interpretation
Initial Tests (lab, imaging)
- Imaging
- Ultrasound (US)
- US is often the first imaging test ordered. It helps distinguish between cysts and solid masses. US may be most helpful in women with very dense breasts; when mammography is needed, a normal US does not negate the need for a mammogram (7)[B].
- Diagnostic mammography with fetal shielding
- The average glandular dose to the breast for a two-view mammogram provides a negligible radiation dose to the fetus (7)[B].
- Magnetic resonance imaging (MRI)
- MRI is used for women who have been diagnosed with breast cancer to better determine the actual size of the cancer and to look for any other cancers in the breast (8,9).
- Test
- After appropriate imaging has been performed, a biopsy should be done for tissue diagnosis unless malignancy has been ruled out.
- If a lesion is clinically questionable, a normal mammogram is insufficient to rule out malignancy and tissue biopsy may still be indicated.
- Do not delay an indicated biopsy because the patient is pregnant. Delay in diagnosis can worsen the prognosis.
- Staging is indicated to rule out metastases: chest x-ray (CXR), liver function tests (LFTs), ± CT Abd/Pelvis (7,8)
Diagnostic Procedures/Other
Nipple discharge exam
- If discharge appears milky or clear green, cancer is very unlikely.
- If discharge is red or red-brown, suggesting that it contains blood, it may be caused by cancer (8).
Treatment
General Measures
- Breast cancer during pregnancy should be diagnosed and treated promptly, using many of the same general principles as in the nonpregnant woman.
- Radiation in breast conservation therapy is avoided in pregnancy because of risk of teratogenicity and induction of childhood malignancies and hematologic disorders. If breast cancer is diagnosed in the 2nd or 3rd trimester, breast conservation can be done with radiation given after delivery.
- Treatment for breast cancer during pregnancy will depend ultimately on the stage of the tumor and trimester.
Medication
- Chemotherapy
- May be used along with surgery (as an adjuvant treatment) for some stages of breast cancer
- In pregnant woman with breast cancer who needs chemotherapy after surgery, chemotherapy is delayed until the 2nd trimester. In the 1st trimester, chemotherapy poses the greatest risk to the fetus during the period of organogenesis. During the 2nd and 3rd trimesters, there is a low incidence of malformation from chemotherapy, although there are other agent-specific risks such as prematurity, intrauterine growth retardation, and low birth weight.
- Antimetabolites such as methotrexate are not given during pregnancy (10)[A].
- Radiation therapy
- Radiation therapy to the breast is often used after breast-conserving surgeries to reduce the risk of the cancer recurrence but is only given after delivery (10)[A].
- High doses of radiation can harm the fetus any time during pregnancy.
- Hormone therapy
- Hormone therapy to block estrogen receptors or stop estrogen production is often used as adjuvant treatment after surgery based on estrogen receptor/progesterone receptor (ER/PR) status. However, it is not used during pregnancy due to a link to birth defects (10)[A].
- Targeted therapy
- Drugs that target HER2, such as trastuzumab, pertuzumab, and Iapatinib, are an important part of the treatment of HER2-positive breast cancers. However, none of these drugs are considered safe for the fetus if during pregnancy.
Issues for Referral
A multidisciplinary team is critical for ensuring that at postpartum, the woman will continue to receive care from her surgeon, oncologist, and obstetrician.
Additional Therapies
Adjuvant therapy
- Adjuvant therapy is given after the primary treatment to lower the risk of cancer recurrence. Adjuvant therapy may include chemotherapy, radiation therapy, hormone therapy, targeted therapy, or biologic therapy.
Surgery/Other Procedures
Two types of surgeries
- Breast-conserving surgeries (surgery followed by radiation)
- Lumpectomy
- Partial mastectomy (3,9)[A]
- Surgeries to remove the entire breast include the following:
- Simple mastectomy
- Modified radical mastectomy (breast and axillary node dissection) (3,9)[A]
Inpatient Considerations
Admission Criteria/Initial Stabilization
Inpatient hospitalization is medically necessary for the administration of chemotherapy for members who meet any of the following criteria:
- Initial dose of chemotherapy while hospitalized for diagnosis of cancer
- Patient receiving chemotherapy that necessitates hydration
- Patient receiving chemotherapy by continuous infusion who do not have central venous access
- Treatment demonstrably causes vomiting severe enough to result in dehydration/hypotension
Ongoing Care
Follow-up Recommendations
- The standard approach for monitoring patients is a physical exam and a review of symptoms ranging from every 3 to every 6 months for the first 2-3 years and every 6 months until year 5, and annually thereafter.
- Continue to have annual mammograms of the other breast (9).
Patient Monitoring
Fetus
- Confirmation of gestational age is critical for treatment planning.
- Assessment of fetal pulmonary maturity may be required if preterm delivery is considered to expedite adjuvant radiation treatment.
Patient Education
As in the nonpregnant patient, when a patient identifies a breast mass, this must promptly be brought to the attention of her physician.
Prognosis
- Breast cancer diagnosed during pregnancy is associated with delayed diagnosis with larger tumors and a greater likelihood of positive lymph nodes at time of diagnosis.
- When all disease characteristics are identical and diagnosis and treatment are prompt, breast cancer during pregnancy has been shown to have the same prognosis as breast cancer in the nonpregnant woman (11,12,13).
Complications
The worst complication is the failure to make the diagnosis, resulting in a delay in diagnosis and a more advanced stage and worse prognosis.
References
1.McMaster J, Dua A, Desai SS, et al. Short term outcomes following breast cancer surgery in pregnant women. Gynecol Oncol. 2013;S0090-8258(13)01177-3.
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2.Schnabel F, Billig J, Cimeno A, et al. Pregnancy-associated breast cancer and increased risk of pregnancy-associated recurrence: a case report. J Med Case Rep. 2012;6:144.
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3.Molckovsky A, Madarnas Y. Breast cancer in pregnancy: a literature review. Breast Cancer Res Treat. 2008;108(3):333-338.
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4.Cullinane CA, Lubinski J, Neuhausen SL, et al. Effect of pregnancy as a risk factor for breast cancer in BRCA1/BRCA2 mutation carriers. Int J Cancer. 2005;117(6):988-991.
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5.Gage M, Wattendorf D, Henry LR. Translational advances regarding hereditary breast cancer syndromes. J Surg Oncol. 2012;105(5):444-451.
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6.Eliassen AH, Hankinson SE, Rosner B, et al. Physical activity and risk of breast cancer among postmenopausal women. Arch Intern Med. 2010;170(19):1758-1764.
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7.Ahn BY, Kim HH, Moon WK, et al. Pregnancy- and lactation-associated breast cancer: mammographic and sonographic findings. J Ultrasound Med. 2003;22(5):491-497.
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8.Ayyappan AP, Kulkarni S, Crystal P. Pregnancy-associated breast cancer: spectrum of imaging appearances. Br J Radiol. 2010;83(990):529-534.
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9.Guidroz JA, Scott-Conner CEH, Weigel RJ. Management of pregnant women with breast cancer. J Surg Oncol. 2011;103(4):337-340.
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10.Litton JK, Theriault RL. Breast cancer and pregnancy: current concepts in diagnosis and treatment. Oncologist. 2010;15(12):1238-1247.
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11.Rugo HS. Management of breast cancer diagnosed during pregnancy. Curr Treat Options Oncol. 2003;4(2):165-173.
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12.McMaster J, Dua A, Desai SS, et al. Short term outcomes following breast cancer surgery in pregnant women. Gynecol Oncol. 2013;S0090-8258(13):01177-3.
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13.Amant F, von Minckwitz G, Han SN, et al. Prognosis of women with primary breast cancer diagnosed during pregnancy: results from an international collaborative study. J Clin Oncol. 2013;31(20):2532-2539.
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Codes
ICD09
- 648.90 Other current conditions classifiable elsewhere of mother, unspecified as to episode of care or not applicable
- 174.9 Malignant neoplasm of breast (female), unspecified
ICD10
- O9A.119 Malignant neoplasm complicating pregnancy, unsp trimester
- C50.919 Malignant neoplasm of unsp site of unspecified female breast
SNOMED
- 609496007 Complication occurring during pregnancy (disorder)
- 254837009 malignant tumor of breast (disorder)
Clinical Pearls
- Any mass in the breast of a pregnant woman must receive the same prompt attention as a mass in a nonpregnant woman.
- Breast cancers diagnosed during pregnancy more often are diagnosed at an advanced stage.
- Radiation is never given during pregnancy, although delivery can be induced early, with subsequent radiation therapy.