Israel Medical Association Journal

Background: Magnetic resonance imaging of the breast has emerged as a valuable imaging tool in addition to conventional imaging modalities. It has high sensitivity for malignant lesions, and can detect mammographically, sonographically and clinically occult cancers. “MR only” lesions are best biopsied under MR guidance; however, this may be a challenging task.

Objectives:  To evaluate our initial clinical experience with MR-guided core needle breast biopsy and MR-guided needle localization.

Methods: We retrospectively evaluated 81 women with 97 lesions, who were scheduled for guided core needle biopsy or MR-guided needle localization followed by surgery. Lesions were categorized as malignant, high risk, or benign according to the BI- RADS MR classification system. MR findings were compared with final histopathology or with follow-up imaging findings.

Results: Fifteen (16%) lesions were malignant (9 invasive ductal carcinoma, 2 invasive lobular carcinoma, 4 ductal carcinoma in situ); 7 (7%) lesions were high risk (4 atypical ductal hyperplasia, 3 radial scars); 75 (77%) lesions were benign, mainly fibrocystic changes. Other benign findings were sclerosing adenosis, pseudoangiomatous stromal hyperplasia, fat necrosis, intraductal papilloma, fibroadenoma, capillary hemangioma, and florid ductal hyperplasia. No major complications were encountered.
Conclusions: MR-guided interventional procedures of the breast are accurate, safe and feasible methods for sampling breast lesions detected only by MR and have become a significant tool in the management of certain patients.

The frequency of pregnancy-associated breast cancer, a rare but serious occurrence, may increase in light of the secular trends for lower parity in general and for an older age at first full-term delivery in particular. Data on PABC[1] in individuals who are at high risk for breast cancer are limited. A computerized search of PUBMED showed that the reported incidence of PABC is 1:3000 pregnancies; it is often diagnosed at an advanced stage and its prognosis is inferior compared to non-PABC. Carriers of mutations in the genes BRCA1/2 may present a specific high risk group for PABC especially at younger ages. Women treated with fertility treatment drugs may be at a higher risk for PABC as well.  

Background: Occult breast cancer without clinically or mammographically detectable breast tumor is an uncommon presentation.

Objectives: To assess the role of breast MRI in women with metastatic carcinoma and an occult primary, and to define the MRI characteristics of the primary breast tumor.

Methods: This retrospective study evaluated 20 women with metastatic carcinoma of unknown origin who underwent breast MRI between 2000 and 2006. Four women were excluded, leaving 16 in the study group. Probability of malignancy was assessed according to BIRADS classification. MRI performance in detecting lesions and evaluating disease extent was assessed, with the gold standard being surgical or biopsy pathology.

Results: MRI detected suspicious lesions in 15 patients. Lesion size ranged from 0.4 to 7 cm (median 1.5 cm). MRI detected a single lesion in 6 patients (40%), multifocal disease in 3 (20%), multicentric disease in 4 (27%), and bilateral breast lesions in 2 (13%). In 13 patients MRI depicted the primary breast cancer. Initial treatment was surgical in nine; MRI correctly estimated disease extent in 6 (67%), underestimated disease extent in 1 (11%), and overestimated it in 2 (22%). Four patients had biopsy followed by chemotherapy; one had multicentric disease and one had multifocal disease. MR findings were false positive in two patients and false negative in one.

Conclusions: MRI is sensitive in detecting the primary tumor and beneficial in assessing tumor extent. Small size and multiple foci are common features. We suggest that bilateral breast MRI be part of the evaluation of women with metastatic carcinoma and an occult primary.
 

Background: Fanconi anemia complementation group C and Bloom syndrome, rare autosomal recessive disorders marked by chromosome instability, are especially prevalent in the Ashkenazi* Jewish community. A single predominant mutation for each has been reported in Ashkenazi Jews: c.711+4A→T (IVS4 +4 A→T) in FACC[1] and BLM^Ash in Bloom syndrome. Individuals affected by both syndromes are characterized by susceptibility for developing malignancies, and we questioned whether heterozygote carriers have a similarly increased risk.

Objectives: To estimate the cancer rate among FACC and BLM^Ash carriers and their families over three previous generations in unselected Ashkenazi Jewish individuals.

Methods: We studied 42 FACC carriers, 28 BLM^Ash carriers and 43 controls. The control subjects were Ashkenazi Jews participating in our prenatal genetic screening program who tested negative for FACC and BLM^Ash. All subjects filled out a questionnaire regarding their own and a three-generation family history of cancer. The prevalence rates of cancer among relatives of FACC, BLM^Ash and controls were computed and compared using the chi-square test.

Results: In 463 relatives of FACC carriers, 45 malignancies were reported (9.7%) including 10 breast (2.2%) and 13 colon cancers (2.8%). Among 326 relatives of BLM^Ash carriers there were 30 malignancies (9.2%) including 7 breast (2.1%) and 4 colon cancers (1.2%). Controls consisted of 503 family members with 63 reported malignancies (12.5%) including 11 breast (2.2%) and 11 colon cancers (2.2%).

Conclusions: We found no significantly increased prevalence of malignancies among carriers in at least three generations compared to the controls.

Background: Germline mutations in BRCA1 and BRCA2 genes account for only 20–40% of familial breast cancer cases. The CHEK2 gene encodes a checkpoint kinase, involved in response to DNA damage, and hence is a candidate gene for breast cancer susceptibility. Indeed, the CHEK2*1100delC truncating mutation was reported in a subset of mostly North European breast cancer families. The rate of the CHEK2*1100delC variant in the Ashkenazi* Jewish population was reported to be 0.3%.

Objectives: To evaluate whether CHEK2 germline mutations contribute to a breast cancer predisposition in Ashkenazi-Jewish high risk families.

Methods: High risk Ashkenazi Jewish women, none of whom was a carrier of the predominant Jewish mutations in BRCA1/BRCA2, were genotyped for germline mutations in the CHEK2 gene by exon-specific polymerase chain reaction followed by denaturing gradient gel electrophoresis and sequencing of abnormally migrating fragments.

Results: Overall, 172 high risk women were genotyped: 75 (43.6%) with breast cancer (average age at diagnosis 49.6 ± 9.6 years, mean ± SD) and 97 asymptomatic individuals (age at counseling 48.3 ± 8.2 years). No truncating mutations were noted and four previously described missense mutations were detected (R3W 1.2%, I157T 1.2%, R180C 0.6% and S428F 5%), one silent polymorphism (E84E 20.5%) and one novel missense mutation (Y424H 1.2%). Segregation analysis of the I157T and S428F mutations (shown to affect protein function) with the cancer phenotype showed concordance for the CHK2*I157T mutation, as did two of three families with the CHK2*S428F mutation.

Conclusions: CHEK2 missense mutations may contribute to breast cancer susceptibility in Ashkenazi Jews.

Background: The imaging parameters that mandate further diagnostic workup in focal asymmetric breast densities are not clearly defined.

Objectives: To identify indications for further workup in FABD[1] by comparing mammographic and ultrasonographic findings with the pathology results of women with FABD.

Methods: Ninety-four women (97 FABD) were referred for core needle biopsy after incidental discovery of FABD on routine mammograms (n=83) or on diagnostic mammograms performed for palpable masses (n=11). Clinical data included patient’s age, use of hormone replacement therapy, family history of breast cancer, and the presence of a palpable mass. Mammograms and sonograms were evaluated for lesion size and location, associated calcifications, architectural distortion, and change from previous examinations when available. Two patient groups emerged according to the pathological findings and the data were compared.

Results: The average age, size and location of the lesions in the malignant (n=5) and benign (n=92) groups were similar. There was a significant difference (P < 0.05) for the presence of a clinically palpable mass (60% vs. 9%, respectively), a cluster of calcifications (60% vs. 12%), associated architectural distortion (exclusively in the malignant group) and a solid mass on sonography (50% vs. 9%). The malignant group had a higher rate of family history of breast cancer and HRT[2] use.

Conclusions: FABD usually present a benign etiology and can safely be managed by follow‑up. The presence of an architectural distortion, a cluster of malignant‑appearing or indeterminate calcifications, a sonographic mass with features of possible malignancy, or a clinically palpable mass mandates tissue diagnosis.

Background: The current methods for pre‑ and post‑chemotherapy examination of the extent of disease in the breast and lymph nodes do not provide sufficiently accurate information and, not infrequently, the surgeon has to re‑operate.

Objectives: To correlate the findings between three methods of examination (physical examination, ultrasonography, mammography), all performed by the same oncologic and radiologic team, in patients with locally advanced breast cancer or a tumor/breast tissue ratio that precludes breast-conserving surgery.

Methods: Forty patients (median age 48 years, range 24–73) with locally advanced breast cancer or with a tumor/breast ratio that precluded breast‑conserving surgery were evaluated by the same medical team and received neoadjuvant chemotherapy. Surgery was performed in all, and the pathologic specimen was correlated with the results of the other examinations.

Results: In the pre‑chemotherapy evaluation, the imaging findings of the breast correlated with the physical findings in 78% of the patients and with the axilla examination in 66.7%. In the post‑chemotherapy analysis, imaging agreed with the physical findings of the breast in 62.2% and in 76.3% of the axilla. Sonography best detected occult breast disease and axillary lymph nodes but correlated with pathology in only 58% of the patients in diagnosing breast tumor and in 65.8% in diagnosing axillary lymph nodes. Mammography correlated with breast and lymph node pathology in half the patients.

Conclusions: None of the classical methods of post‑neoadjuvant chemotherapy evaluations could adequately delineate the actual extent of the disease in the breast and axillary lymph nodes. More exacting techniques of imaging combined with the classical methods are required.