Gestational or pregnancy-associated breast cancer

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. Up to 20 percent of breast cancers in women under age 30 are pregnancy associated

The patient was a 32 year old female past medical history who presented to breast clinic due to breast lump. At time of presentation patient was in the 3rd trimester of her 4th pregnancy (G4P3). She first noticed the palpable mass 1 month prior. Patient had ultrasound evaluation of both breasts prior to clinic visit in which showed 2.8 x 1.8 x 2.7 cm irregular mass at the 8 o’ clock position 7 to 8 cm from the nipple of the right breast

Exam was positive for a palpable mass in the right breast located in the lower outer quadrant measuring 2.5 cm. The mass was mobile and well circumscribed. No skin changes or nipple discharge were noted. The right axilla was without lymphadenopathy. Exam was also positive for a gravid abdomen consistent with gestational age for her 3rd trimester

Primary tumor  The physiologic changes in the breast that accompany pregnancy (eg, engorgement and hypertrophy) make physical examination more challenging, interpretation of findings more difficult, and may limit the utility of mammography

Mammography  Mammography is not contraindicated in pregnancy as the average glandular dose to the breast for a two-view mammogram (200 to 400 millirad) provides a negligible radiation dose to the fetus as long as abdominal shielding is used

Ultrasonography  Breast ultrasonography can determine whether a breast mass is a simple or complex cyst or a solid tumor without the risk of fetal radiation exposure and may be used to guide the diagnostic biopsy. A focal solid mass is observed in the majority of cases of gestational breast cancer

Breast MRI Gadolinium-enhanced MRI appears to be more sensitive than mammography for detecting invasive breast cancer, particularly in women with dense breast tissue. Studies demonstrate potential fetal harm with gadolinium exposure in the first trimester Gadolinium should therefore be avoided during pregnancy if possible

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 excisional biopsies can be performed relatively safely during pregnancy, preferably under local anesthesia Needle core biopsy is the preferred method.

No masses were seen in the left breast No masses were seen in the left breast. She then underwent ultrasound guided core biopsy of the right breast. Pathology showed invasive ductal carcinoma (Grade III, moderate to poorly differentiated) with a malignant stromal component consistent with metaplastic carcinoma (carcinosarcoma). Receptors were ER, PR and Her2 negative.

PATHOLOGIC FEATURES The majority of breast cancers in pregnant women are infiltrating ductal adenocarcinomas as in nonpregnant women. However, pregnancy-associated breast cancers are predominantly poorly differentiated and diagnosed at an advanced stage, particularly in those diagnosed while lactating

Hormone receptor expression  Most series report a lower frequency of estrogen receptor and progesterone receptor expression in pregnancy- associated breast cancer compared with breast cancer in nonpregnant patients (approximately 25 versus 55 to 60 percent)

It was decided that the patient should undergo neoadjuvant chemotherapy as soon as possible as she was in the 3rd trimester.

Staging Chest computed tomography (CT) scans are generally avoided during pregnancy If further evaluation of the chest is warranted, an MRI of the thorax is preferred.  Abdominal ultrasound for the evaluation of liver metastases is a safe procedure in pregnant women but is significantly less sensitive than CT or MRI MRI without contrast is preferred if further visceral organ evaluation is required Bone evaluation — Radionuclide bone scans are reported to be safe during pregnancy

MONITORING OF THE PREGNANCY The pregnant woman with breast cancer requires careful and continuous monitoring of her pregnancy by her obstetrician (often a specialist in maternal and fetal medicine) and her oncologist. Confirmation of gestational age and expected date of delivery are important as both are significant factors in treatment planning. Amniocentesis may be required to determine pulmonary maturity if early delivery is being considered

Systemic therapy   The data suggest it is safe to administer many agents used in the treatment of breast cancer during pregnancy when initiated after the first trimester, and that the majority of pregnancies result in live births with low related morbidity in the newborns The most data available are with anthracycline-based chemotherapy, often on an every-three-week schedule. Taxanes appears feasible and safe during the second and third trimesters of pregnancy, with minimal maternal, fetal, or neonatal toxicity  The use of trastuzumab during pregnancy is contraindicated. The use of selective estrogen receptor modulators (SERMs) such as tamoxifen during pregnancy is generally avoided

Timing of chemotherapy  For pregnant breast cancer patients who need chemotherapy treatment, clinicians should advise against a delay in the initiation of systemic chemotherapy once the pregnancy has safely reached the second or third trimester Care needs to be taken to avoid exposing the fetus to chemotherapy during the first trimester, and to stop chemotherapy prior to delivery so that the mother and infant are not experiencing treatment-related toxicities in the delivery or postpartum stages

She then received 4 cycles of Adriamycin and Cytoxan. Roughly at the end of the chemotherapy treatment the patient had a repeat breast ultrasound which showed the mass to be increased in size to 5.1 x 3.7 x 5.1 cm

Locoregional treatment  The same local treatment options that are available for nonpregnant patients should be considered in pregnant women, with the exception of radiation therapy (RT)

Mastectomy   Mastectomy may be chosen when the patient opts to continue the pregnancy, even for women with clinical anatomic stage I and II disease An advantage of mastectomy may be the elimination of the need for breast RT

Breast-conserving surgery  The therapeutic equivalence of mastectomy and breast-conserving therapy (breast-conserving surgery [BCS] followed by RT) has been demonstrated in nonpregnant women; this is also true for the pregnant patient. BCS can be used effectively as RT can be delayed after the administration of adjuvant or neoadjuvant chemotherapy.

Radiation therapy Radiation should be delayed whenever possible until after delivery.

Management of the axilla The use of sentinel lymph node biopsies during pregnancy is controversial, with case series demonstrating increasing evidence of safety and efficacy in pregnant patients Therefore, axillary lymph node dissection should be considered as standard approach.

she was taken for a right skin sparing mastectomy with right axillary sentinel lymph node biopsy and placement of tissue expander. Of the 3 sentinel lymph nodes taken all were negative. Final pathology of the mass showed metaplastic carcinoma (carcinosarcoma). The epithelial component was invasive ductal carcinoma grade III/III (Mitotic rate 3, Nuclear pleomorphism 3, Glandular/Tubular differentiation 2, Histologic grade 3) and the mesenchymal component was poorly differentiated sarcoma. The mass was 6.2 cm at the widest diameter with necrosis and areas of infarct present. Final tumor stage was pT3N0Mx, Stage IIB, ER (+) (<5%), PR (-), Her2 (-). Patient had genetic testing and was found to be BRCA (-).

Timing of delivery  Delivery should occur following the mother's white blood cell count and platelet count nadir to reduce the potential risk of infectious complications and bleeding from thrombocytopenia. Chemotherapy should be avoided for three to four weeks before delivery to avoid transient neonatal myelosuppression and potential complications of sepsis and death whenever possible.

Elective termination of pregnancy The decision to continue or terminate the pregnancy should be individualized and made by a fully informed woman in conjunction with her clinician. Early termination of pregnancy does not improve the outcome of gestational breast cancer

Maternal health   Contemporary studies that specifically evaluated the outcomes of women diagnosed with breast cancer during pregnancy have consistently shown that there is no negative impact on survival

PREGNANCY AFTER BREAST CANCER Pregnancy in breast cancer survivors did not significantly impact survival and suggested that pregnancy after breast cancer may have a protective effect It is common for clinicians to advise women to wait for at least two years before contemplating pregnancy The primary reason for this recommendation is that most recurrences of breast cancer occur within the first two years after initial diagnosis and treatment

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