| | Imaging of pregnancy-associated breast cancerWith pregnancy coming later and later in a woman's life, breast cancer during gestation or postpartum may be seen more often. In this context, the imaging techniques commonly used to diagnose and treat cancer offer unique challenges.
▪During pregnancy it is important to maintain breast examination routines.
▪The physiological changes to the breasts during pregnancy and lactation and the risks to the fetus limit the usefulness of mammograms and MRI.
▪Ultrasound imaging is the best starting point to manage breast cancer during pregnancy because of its low health risks and because of its usefulness in guiding core biopsies.
During pregnancy and lactation, a woman's breasts undergo dramatic changes. The breast tissue begins to respond to hormonal influence already in the first trimester and, as gestation progresses, lobular acini proliferate and lobules expand with secreted fluid in preparation for lactation. The woman may experience pain and tenderness and may develop lumps and nodules. Considering these changes, pre-natal care must involve the physical examination of the breasts and breast self-examination. A palpable finding that is distinct from the other widespread changes in the breast warrants further evaluation. A new or growing lump should be investigated through imaging.
Pre-natal breast examination is important because breast cancer during pregnancy, though uncommon, usually presents as a painless lump or as another physical finding. However, because of the underlying changes to the breast, it may be more difficult to recognize a significant palpable abnormality. In most cases breast lumps are caused by benign or normal processes. During pregnancy and lactation the most common findings are growing fibroadenomas, lactating adenomas, and galactoceles. Much of the time, palpable findings are caused by normal changes in the architecture of the breast tissue.1
“Pregnancy-associated breast cancer” is defined as breast cancer occurring during pregnancy or during the first year postpartum.2 Rivaled only by cervical cancer, the frequency of breast cancer in pregnancy is approximately 1 in 3000 to 10,000 gestations and accounts for 2–3% of all breast cancers.3 Breast cancer during pregnancy appears to be coincidental and there is no reason to suspect that pregnancy or lactation cause or accelerate the disease. In terms of survival, when matched for stage of malignancy, patients with pregnancy-associated breast cancer show no statistical difference compared to those with breast cancer that is not associated with pregnancy.4
Early detection of breast cancer is just as important during pregnancy as it is in general. However, during pregnancy, physical examination and breast self-examination are usually the only available modes of surveillance. It is generally accepted that women who are pregnant, even if they are old enough to merit annual mammography screening, will forgo this procedure during pregnancy. The normal changes in the breasts of pregnant and lactating women often interfere with the sensitivity of the physical examination. Although these women are monitored regularly by a health care provider and are more likely to be conscious of the changes in their breasts, they are also more liable to diagnosis with breast cancer at more advanced stages.5
When there is a palpable finding that warrants further investigation, the physician does have the option of performing fine needle aspiration cytology (FNAC). However, the specificity of FNAC is especially limited in the pregnant patient because of the added challenge of distinguishing hormone-related cellular atypia from malignancy.6 Palpable abnormalities also warrant an imaging evaluation. The imaging modalities for assessment of breast cancer generally include ultrasound, mammography and magnetic resonance imaging (MRI). In addition, image guided core biopsies can help obtain histological diagnoses. However, for a pregnant patient, any imaging strategy must be tailored.
Ultrasound  Ultrasound imaging of a palpable physical finding dependably shows the presence of a lesion or malignancy that is distinct from a background of dense breast tissue. In four separate series, all pregnancy-associated breast cancers were visualized on ultrasound.7, 8, 9, 10 Ultrasound makes it possible to examine the morphology of a lesion but, more important, it can be used to target the abnormality visually and perform a core biopsy for histological diagnosis. Ultrasound is also valuable to monitor the response to chemotherapy during pregnancy.7 Mammography The greater density of the breast tissue and the prominence of the ductal pattern caused by the increase in fluid in the parenchyma and ducts during pregnancy and lactation all limit the use of mammography. Nonetheless, most cancers are visible with this modality.7 Concerns about radiation often cause hesitation in using mammography for a pregnant patient. In actuality it is possible to shield the patient and to protect the fetus if mammography is warranted. A standard bilateral two-view mammogram exposes the fetus to only 0.004 Gy of radiation.11 The exposure of the fetus to radiation is minuscule and is of even less concern in the third trimester. Mammography remains important because of its ability to show suspicious calcifications. Breast MRI MRI of the breast is not done during early pregnancy because of the risk of exposing the fetus to high magnetic fields and to gadolinium-based MRI contrast. In late pregnancy it is difficult for the patient to assume the prone position for enough time to acquire the images. If the patient is diagnosed late in pregnancy and delivers before starting treatment, the MRI can be used for staging evaluation. During lactation, an MRI can be done but the milk should be pumped and discarded for 48 hours after the procedure because the gadolinium-based contrast is excreted into the milk. Breast MRI during lactation is limited by the prominent contrast enhancement of normal glandular tissue. because this enhancement can be similar to that seen in malignant tissue. Still, MRI can often be helpful in identifying the extent of the index lesion and may reveal the presence of additional unsuspected lesions in the breasts.10 The following case reports on pages 62, 63 and 64, illustrate the role of breast imaging in the evaluation of pregnancy-associated breast cancer. When a pregnant woman is diagnosed with breast cancer, the treatment options are complex; they depend on age of gestation, on the extent of malignancy, and, importantly, on patient preferences. Early in pregnancy, there may be the option to terminate the pregnancy; but this may not be necessary because breast cancer can be treated during gestation.4, 12 Later in pregnancy, there is the option of waiting until after delivery to begin treatment. The relative risk of developing axillary metastases as a result of delayed treatment of breast cancer during pregnancy has been quantified on the basis of the doubling times of tumors. The daily increased risk is in the range of 0.028% to 0.057%, and may be considered acceptable to some third-trimester pregnant women with early stage breast cancer who prefer breast conserving therapy after delivery to a mastectomy during pregnancy.13
JH was 39 weeks pregnant with her second child when she saw a mass in her left breast while looking in the mirror. Her obstetrician ordered a breast ultrasound that showed a solid 1.3 cm lesion (Figure 1A) and a biopsy was performed the same day. The pathology report identified poorly differentiated estrogen receptor (ER) negative, progesterone receptor (PR), and Her2 receptor negative ductal carcinoma, within an intramammary lymph node. Three days after the biopsy she scheduled a caesarean section and delivered a healthy girl.
Her risk factors for breast cancer include: menses that started at the age of 14; a first full term pregnancy through IVF at the age of 32, a maternal grandmother diagnosed with breast cancer in her 70's, and being of Ashkenazi decent.
While recovering in the hospital, she underwent a breast MRI, followed by mammogram and ultrasound. The MRI found a 2.5 cm primary lesion in the mid-upper portion of the left breast (Figure 1B), with 3 satellite lesions involving the whole upper aspect of the left breast. The intramammary node was also identified.
The mammogram was limited because of the dense post-partum breast tissue and suggested a density in the CC view, medial to the nipple (Figure 1C).
Ultrasound described the primary lesion as a 2.3 cm lesion above and medial to the nipple. A second lesion was seen above the nipple that measured 0.9 cm. Both lesions were biopsied and had an identical pathology to the first biopsy.
The CT scans for metastatic workup—bone, chest and abdominal—were negative.
The patient had bilateral mastectomies with immediate reconstruction. At the time of surgery, the lymph nodes in the left axilla were grossly positive resulting in a full node dissection.
Her final pathology was most consistent with the MRI. The primary lesion in the medial upper aspect of the breast measured 3.4 cm with two additional satellites measuring 0.9 cm and 0.4 cm. The intramammary node had a 1.9 cm focus of carcinoma with an additional seven out of nine nodes positive for carcinoma. One year later the patient is disease free.
CB was 32 weeks pregnant with her second child when she noted a mass in her right breast. Two weeks later her obstetrician sent her to our breast center where she had an ultrasound and an exam with a surgeon.
The ultrasound showed a 2.5 cm spiculated mass in the palpable area (Figure 2A). An additional nonpalpable round 0.8 cm nodule was noted more medially. Both lesions were biopsied with ultrasound guidance. The pathology report showed that the 2.5 cm lesion was a poorly differentiated ER, PR negative, Her2 positive ductal carcinoma. The smaller lesion was a fibroadenoma.
Her risk factors for cancer include: menses at the age of 12, a first full-term pregnancy at the age of 33, a great aunt with breast cancer in her 80's, and possibly a maternal grandmother with breast cancer. She is not of Ashkenazi decent, has no genetic risk factors and did not use hormones pre-pregnancy.
At 37 weeks she was induced, delivered a healthy girl and afterwards had a mammogram and an MRI. The mammogram was limited because of the dense glandular breast tissue (Figure 2B). The MRI confirmed the known malignancy in the lateral breast and measured it slightly larger at 3.3 cm. The fibroadenoma was also noted. A single 1.1 cm lymph node in the right axilla was suspiciously enlarged (Figure 2C).
One week later she underwent a lumpectomy and axillary node dissection. At the time of surgery her nodes were grossly positive. The final pathology revealed a 3.4 cm primary tumor with 10 out of 18 nodes positive for malignancy. Her subsequent metastatic work up was positive for bone and liver metastases.
She tolerated her chemotherapy well and is currently undergoing radiation therapy.
EE was 37 weeks pregnant with her third child when she felt a mass in her left breast. Her obstetrician ordered an ultrasound that showed a 1.1 cm lesion with punctate calcifications (Figure 3A). A biopsy was performed the same day and revealed a poorly differentiated ER, PR Her2 positive, ductal carcinoma. There was no evidence of lymphovascular invasion on the core biopsy.
Her risk factors for cancer include: menses at the age of 12 and first full term pregnancy at the age of 34. She has no family history of breast or ovarian cancer and is not of Ashkenazi decent. The patient was induced 2 weeks later and delivered a healthy boy. The following day she had an MRI and mammogram. The MRI was limited due to the postpartum physiologic changes to both breasts (Figure 3B). The mammogram identified a 5 cm wedge of calcifications extending along a transverse plane from the nipple to the lateral breast where it was 2 cm wide (Figure 3C). The metastatic work-up was negative.
The patient underwent a mastectomy with delayed reconstruction. She had grossly positive nodes and had a complete axillary node dissection. Her final pathology report revealed a multifocal moderately differentiated ductal carcinoma, measuring 2 cm and 0.9 cm. There was an additional 0.3 cm focus of invasive lobular carcinoma in the inferior aspect of the breast. She also had 5.5 cm of high grade DCIS with calcifications surrounding the tumor. Ten out of nineteen nodes were positive for metastatic disease.
The patient is currently undergoing chemotherapy.
The management of breast lumps during pregnancy and lactation should begin with ultrasound examination. In terms of imaging this is the most sensitive modality and represents no risk to the woman or to the fetus. Furthermore, if there is an abnormality, the ultrasound can guide a core biopsy. The information from mammography during pregnancy may be important to plan treatment and to determine staging (Figure 3C). If done with proper shielding the exposure to the fetus is minimal. The value of MRI in pregnancy-associated breast cancer is limited by the increased vascularity and consequent contrast enhancement of normal tissue limiting sensitivity of the examination. (Figure 3B). The relative safety of MRI to the fetus is also of concern because of the exposure to high magnetic fields. As mentioned previously, the gadolinium contrast adds risk since it crosses the placenta and is potentially teratogenic.12 If the choice is made to deliver the baby before starting cancer treatment, mammography and MRI can be performed following delivery. MRI of the breasts after delivery can be performed safely and may yield valuable information not apparent on mammography and subtle on ultrasound (Figure 1B). With the modern tendency to delay childbearing, there is a strong probability that the frequency of breast cancer in pregnancy will grow based solely on the increased risk of breast cancer with age. Detecting pregnancy-associated breast cancer still depends on attentive and thorough physical examination. Patients should also be encouraged to perform breast self-examination since they are commonly the ones to recognize the presence of a lump. If there are palpable findings during pregnancy, the imaging assessment should begin with ultrasound to determine whether any further diagnostic measures are warranted. References 1.
1
Hogge JP
, de Paredes ES
, Magnant CM
, Lage J
.
Imaging and management of breast masses during pregnancy and lactation
.
The Breast Journal
. 1999;5:272–283
.
CrossRef
2.
2
Petrek J
.
Breast Cancer during pregnancy
.
Cancer
. 1994;74(suppl 1):518–527
.
3.
3
Antonelli NM
, Dotters DJ
, Katz VL
, Kuller JA
.
Cancer in pregnancy: a review of the literature. Part I-II
.
Obstet Gynecol Surv
. 1996;51:125–142
.
MEDLINE |
CrossRef
4.
4
Ring AE
, Smith IE
, Ellis PA
.
Breast cancer and pregnancy
.
Annals of Oncology
. 2005;16:1855–1860
.
MEDLINE |
CrossRef
5.
5
Zemlickis D
, Lishner M
, Degendorfer P
, et al.
Maternal and fetal outcome after beast cancer in pregnancy
.
Am J Obstet Gynecol
. 1992;166:781–787
.
MEDLINE 6.
6
Novotny DB
, Maygarden SJ
, Shermer RW
.
Fine needle aspiration of benign and malignant breast masses associated with pregnancy
.
Acta Cytol
. 1991;35:676–686
.
MEDLINE 7.
7
Yang WT
, Dryden MJ
, Gwyn K
, Whitman GJ
, Theriault R
.
Imaging of breast cancer diagnosed and treated with chemotherapy during pregnancy
.
Radiology
. 2006;239:52–60
.
MEDLINE |
CrossRef
8.
8
Liberman L
, Giess CS
, Dershaw DD
, Deutch BM
, Petrek JA
.
Imaging of pregnancy-associated breast cancer
.
Radiology
. 1994;191:245–248
.
MEDLINE 9.
9
Ahn BY
, Kim HH
, Moon WK
, et al.
Pregnancy- and lactation-associated breast cancer: mammographic and sonographic findings
.
J Ultrasound Med
. 2003;22:491–497
.
MEDLINE 10.
10
Espinosa LA
, Daniel BL
, Vidarsson L
, Zakhour M
, Ikeda DM
, Herfkens RJ
.
The lactating breast: contrast-enhanced MR imaging of normal tissue and cancer
.
Radiology
. 2005;237:429–436
.
MEDLINE |
CrossRef
11.
11
Nicklas AH
, Baker MD
.
Imaging strategies in the pregnant cancer patient
.
Semin Oncol
. 2000;27:623–632
.
MEDLINE 12.
12
Woo JC
, Yu T
, Hurd T
.
Breast cancer in pregnancy: a literature review
.
Arch. Surg.
. 2003;138:91–98
.
MEDLINE |
CrossRef
13.
13
Nettleton J
, Long J
, Kuban D
, Wu R
, Shaeffer J
, El-Mahdi A
.
Breast cancer during pregnancy: quantifying the risk of treatment delay
.
Obstet Gynecol
. 1996;87:414–418
.
MEDLINE |
CrossRef
Tufts University School of Medicine, Newton Wellesley Hospital, Newton, MA  Tufts University School of Medicine, Newton Wellesley Hospital, Washington Street, Newton, MA 02462
PII: S1546-2501(06)00021-1 doi:10.1016/j.sram.2006.08.002 © 2006 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved. | |
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