breast cancer in pregnancy sadaf alipour assistant professor general surgeon tehran university of medical sciences

INTRODUCTION  Gestational or pregnancy-associated breast cancer is defined as breast cancer that is diagnosed during pregnancy, in the first postpartum year, or any time during lactation.

a challenging clinical situation Welfare of both mother and fetus must be taken into account in any treatment planning Prospective studies are very few Much of the clinical evidence is limited to retrospective case series and case reports.

incidence One of the most common cancers in nonpregnant and pregnant women Up to %20 of BCs under 30 are Py-associated Fewer than %5 of BCs diagnosed under 50 are detected during Py or in postpartum

A relatively uncommon event. Incidence: 15-35 per 100,000 deliveries epidemiology A relatively uncommon event. Incidence: 15-35 per 100,000 deliveries Fewer cases during Py than in first postpartum year Incidence appears to be increasing as more women delay childbearing

Pathology Majority : infiltrating ductal carcinomas, as in nonpregnants But predominantly poorly differentiated and advanced stage, esp. those in lactation May higher incidence of inflammatory breast cancer than nonpregnants Most series report lower frequency of ER and PR compared to nonpregnants(% 25 versus %55- 60)

presentation Usually present similarly to nonpregnants Mass or thickening in the breast Rarely, a nursing infant has refused a breast that harbors an occult carcinoma, leading to an early diagnosis of breast cancer; this has been named the milk rejection sign

Diagnosis (1) Physiologic changes in the breast in pregnancy (eg, engorgement and hypertrophy) make examination more challenging, interpretation of findings more difficult, and limit the utility of mammography Diagnostic delays of 2m or longer common Such delays may adversely impact outcome, since even a one month delay in diagnosis can increase the risk of nodal involvement by 1 to 2 percent Index of suspicion for cancer must be high in Py with a breast mass

Diagnosis (2) Index of suspicion for cancer must be high in Py with a breast mass A breast mass that persists for more than two weeks should be investigated, although the majority (80 percent) will be benign

Differential diagnosis A breast mass in a pregnant or lactating woman can be: breast cancer, lactating adenoma, fibroadenoma, cystic disease, lobular hyperplasia, milk retention cyst (galactocele), abscess, lipoma, hamartoma, and rarely, leukemia, lymphoma, phyllodes tumors, sarcoma, neuroma, or tuberculosis

Not contraindicated in pregnancy Mammography (1) Not contraindicated in pregnancy Average dose to breasts for a two-view mammogram (200 to 400 millirad) provides a negligible radiation dose to the fetus Abdominal shielding is recommended.

Sensitivity is altered by changes of pregnant or lactating breasts: Mammography (2) Sensitivity is altered by changes of pregnant or lactating breasts: increased water content, higher density loss of contrasting fat Nevertheless, data suggest that mammography is sufficiently sensitive to diagnose breast cancer during pregnancy and lactation

ultrasonography Often the first imaging test ordered to evaluate a breast mass in a pregnant woman Determines simple or complex cysts or solid tumors without risk of fetal radiation exposure A focal solid mass is observed in majority of gestational BCs

MRI (1) Not systematically studied for gestational breast masses No harmful effects from MRI during pregnancy have been reported But the National Radiological Protection Board avoids it in T1 if possible since limited experience during organogenesis However, MRI considered in T1 when benefits exceed risks

Mri (2) Gadolinium-enhanced MRI more sensitive than mammography for detecting invasive breast cancer, esp. with dense breasts But gadolinium avoided in pregnancy due to potentially long half-life in fetus and lack of safety information. Gadolinium-enhanced breast MRI may be considered in postpartum

Biopsy  A clinically suspicious breast mass requires biopsy for definitive diagnosis, regardless of whether or not a woman is pregnant, and despite negative mammographic or ultrasound findings. Core, incisional, or excisionalBx relatively safe during Py, preferably under LA

Lymph nodes Debate over safety and efficacy of sentinel lymph node biopsy in Py-associated BC Areas at risk for and/or clinically suspicious for LAP should be further evaluated with US and FNA

Systemic staging Tendency to Dx at advanced stage As in nonpregnants, locally advanced stage BC [stage III or IV ] and/or suspicious symptoms should prompt complete staging In contrast, if asymptomatic and clinically node-negative and early stage, no need for evaluation of lung, liver, bone, or brain metastases

lung metastases For lung metastases: CXR with abdominal shielding Estimated dose to the fetus :0.06 millirad. Ability to evaluate lower lung parenchyma with CXR limited late in gestation when gravid uterus pressing against diaphragm. CTscan generally avoided in Py because of the large cumulative radiation dose with multiple slices If further evaluation of chest warranted:MRI preferred but gadolinium avoided

 liver metastases US safe for evaluation in Py but significantly less sensitive than CT or MRI CT of abdomen or pelvis not performed in Py MRI preferred if further visceral organ evaluation required National Radiological Protection Board advises MRI be avoided in T1 if possible

If suspected: MRI the safest and most sensitive way Brain metastases If suspected: MRI the safest and most sensitive way Information regarding safety and efficacy of PET in Py limited

Bone evaluation: Radionuclide bone scan Safe in Py. A "low-dose" bone scan described that exposes fetus to 0.08 rad as compared to the standard 0.19 rad for a conventional bone scan Fetal exposure may also result from proximity to radionuclides excreted in bladder: Maternal hydration and frequent voiding can reduce this exposure. Not recommended in absence of signs or symptoms of bone abnormality.

Bone evaluation:skeletal MRI May be considered as alternative to bone scan, (without contrast until further safety data are available). Since breast metastases are deposited in red marrow, imaging of axial skeleton (spine, pelvis, ribs and sternum) include approximately %80 of all metastatic sites Alternatively, screening MRI of thoracic and lumbar spine may be considered if no complaints of extraspinal bony metastases The safety of plain skeletal radiographs is unclear. Although these films result in less than 1 rad exposure to the fetus and have been obtained during pregnancy by obstetricians for pelvimetry measurements and to evaluate for renal stones, even low levels of ionizing radiation may increase the risk of childhood leukemia

Bone evaluation: Alkaline phosphatase Increases markedly during Py due to placental production Cannot be used as indicator of bone metastases Even bone specific ALP is not a reliable measure of bone disease.

monitoring of pregnancy The pregnant woman with BC requires careful and continuous monitoring of her Py by her obstetrician Confirmation of gestational age and EDC important Aniocentesis may be required to determine pulmonary maturity if early delivery is being considered.

note: Early termination of Py does not improve survival of gestational BC and some series suggest a decreased survival associated with early termination of Py Indications of local and systemic adjuvant therapy are similar to non- pregnants Herceptin and endocrine therapy are not safe during any trimester of Py. When these therapies are administered post- partum, breast feeding should be avoided

SUMMARY AND RECOMMENDATIONS Gestational or Py-associated BC is a BC diagnosed in Py, 1st postpartum year, or any time during lactation A relatively uncommon event although one of the most common cancers in Py Incidence increasing as more women delay Py Predominantly poorly differentiated and advanced Index of suspicion for cancer must be high in Py with a breast mass Breast US and mammo in any suspicious mass Clinical suspicion requires Bx for definitive Dx

references 1- Schwartz Principles of Surgery (book) 2- Diseases of the Breast (book) 3-UptoDate (online)

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