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The feasibility of large-core-needle magnetic resonance imaging (MRI)-guided breast biopsy at 3 T was assessed. Thirty-one suspicious breast lesions shown only by MRI were detected in 30 patients. Biopsy procedures were performed in a closed-bore 3-T clinical MR system on a dedicated phased-array breast coil with a commercially available add-on stereotactic biopsy device. Tissue sampling was technically successful in 29/31 (94%) lesions. Median lesion size (n = 29) was 9 mm. Histopathological analysis showed 19 benign lesions (66%) and one inconclusive biopsy result (3%). At follow-up of these lesions, 15 lesions showed no malignancy, no information was available in three patients and two lesions turned out to be malignant (one lesion at surgical excision 1 month after biopsy and one lesion at a second biopsy because of a more malignant enhancement curve at 12-months follow-up MRI). Nine biopsy results showed a malignant lesion (31%) which were all surgically removed. No complications occurred. MRI-guided biopsy at 3 T is a safe and effective method for breast biopsy in lesions that are occult on mammography and ultrasound. Follow-up MRI at 6 months after the biopsy should be performed in case of a benign biopsy result.

Background: In 2003, for the first time, US breast cancer incidence rates have fallen. Experts argue whether this is due to the reduced uptake of screening mammography or to lower use of Hormone Replacement Therapy (HRT). This study aims to disentangle the respective impact of screening and HRT on age-incidence rates and histology of breast cancer, by comparing two populations with comparably high levels of screening mammography, but with different prevalence of HRT., Methods: We included all invasive breast cancers recorded at the Geneva cancer registry (n = 4,909) and the Netherlands Cancer Registry (n = 152,428) between 1989-2003. We compared age-specific incidence rates and trends in histological subtyping between the two populations., Results: Between 1989-1991, incidence rates increased with age in both populations. In 2001-2003, women aged 60-64 years showed highest incidence rates in Geneva, while in the Netherlands incidence rates continued to increase with age. The annual increase in ductal cancer incidence was similar in the Netherlands (2.3%) and Geneva (2.5%), but the annual increase in lobular cancer was sharper in Geneva (10%) than in the Netherlands (5%)., Conclusion: The sharp differences in age distribution and histological subtyping of breast cancer between two European populations are not attributable to screening, since both populations have a high uptake of mammography screening. Since the prevalence of HRT use is very high in Geneva and rather low in the Netherlands, HRT may explain these discrepancies. However, other etiological factors and differences in histological assessment may also have played a role.

Purpose: To report the accuracy of magnetic resonance imaging (MRI)-guided needle localization for diagnosis of MRI detected suspicious breast lesions located in difficult accessible regions of the breast, using the freehand method in a 3.0 T closed bore magnet., Materials and Methods: In five patients with five MRI-only breast lesions underwent MRI-guided needle localization for histopathologic evaluation of the lesions. All interventional procedures were performed in a 3.0 T MRI system with the patient in prone position and by using a dedicated phased array breast coil. MRI-guided needle localizations were performed by using a freehand technique. In our study, the high-resolution scan allowed preprocedural localization of all lesions without use of contrast enhancement. In all cases contrast-enhanced MRI was performed after insertion of the wire to confirm the tip of the wire in direct contact with the enhancing lesion., Results: Needle localizations were performed in five patients. Histopathologic evaluation of tissue after surgery excision biopsy revealed one lymph node, three invasive ductal carcinoma and one ductal carcinoma in situ. Lesion size varied from 6 to 30 mm. Mean duration time was 25 min. No complications occurred during the intervention method. In the patient with the benign lesion control MRI of the breast after 6 months confirmed lesion removal., Conclusions: MRI-guided needle localization by using a freehand technique in a 3.0 T closed bore magnet is a safe and accurate method for diagnosis of difficult accessible breast lesions only visible on MRI.

Introduction: Seeding of biopsy needle tracks with viable malignant cells was an initial concern with all diagnostic breast needle procedures, including 14G automated needle biopsy. In an attempt to further evaluate this phenomenon, we have addressed the following questions: (1) are the tracks left by the needle biopsy procedure detectable in the surgical excision specimen? (2) Are displaced tumour cells visible along the needle tracks? (3) Is it possible to identify and excise the entire needle track for thorough histopathologic evaluation?, Methods: Surgical biopsy specimens of patients previously diagnosed with cancer on stereotactic 14G-needle biopsy were studied to find needle tracks. These are characterised by hemosiderin, scar tissue, foreign body giant cell reaction, fat necrosis, or organizing haemorrhage. Occurrence of displaced tumour cells or groups of cells along the tracks was registered., Results: Needle tracks were found in 22/64 excision specimens of patients who underwent 14G-needle biopsy and surgery on the same day. Tumour-cell displacement along the needle track was seen in 11/22 cases (50%). In a prospective study, an attempt was made to excise the entire needle track in 13 consecutive cancer cases after 14G biopsy. Median time interval between core biopsy and first surgical excision was 21 days (range 7-35). Needle tracks could be visualised in 11/13 cases; displaced cells were seen in seven., Conclusion: Needle tracks can be found in the excision specimens of patients who previously underwent 14G biopsy, and displaced tumour cells can be recognised. Excision of the entire needle track is neither feasible, nor advisable as a routine measure, since radiotherapy is advised for both in situ and invasive carcinoma after conservative surgery.

Aromatase inhibitors are proving to be more effective than tamoxifen for postmenopausal patients with breast cancer. Estrogen concentrations in the breast are similar in both premenopausal and postmenopausal women, and several fold higher than circulating levels in postmenopausal women. In order to investigate the importance of intratumoral aromatase in stimulating the proliferation of the tumor, we used immunocytochemistry to determine the extent of aromatase expression in relationship to the response of the patient to aromatase inhibitor treatment. The relationship between positive staining for aromatase in the primary tumor and response to treatment with an aromatase inhibitor was investigated in a retrospective study of 102 patients with advanced breast cancer. Immunohistochemical staining using a monoclonal antibody against aromatase was performed on paraffin embedded tumor tissue. Response was evaluated using UICC criteria. Nine out of 13 patients with objective response to treatment stained positive and 49 of 89 patients with stable or progressive disease stained positive. No significant relationship between positive staining and objective response to treatment could be found. When patients with 'clinical benefit' (i.e. objective response plus prolonged stable disease of at least 6 months) were considered, also no relationship could be found. Further analysis of subgroups with positive hormone receptors, treatment with newer generation aromatase inhibitors, single metastatic site, non-visceral metastases and previous treatment only with tamoxifen did not show any relationship. Tumor aromatase expression did not correlate with response of patients with advanced breast cancer to aromatase inhibitor treatment. Most patients had relapsed from other treatments before receiving an aromatase inhibitor. It seems likely that many of these patients had tumors that may have progressed to hormone independence at this stage of the disease. Research in patients who have received treatment with aromatase inhibitors in earlier stages of disease (first line and adjuvant treatment) may provide further information on the relationship between tumor aromatase, steroid receptors and response to inhibitor treatment.

The purpose of this study was to assess whether general pathologists are able to make as accurate and reproducible a diagnosis on large-core needle biopsies as on open breast biopsy specimens. A total of 688 patients underwent a stereotactic large-core (14G) needle biopsy and subsequent surgical excision of 718 non-palpable breast lesions. Forty-two pathologists from 10 departments of pathology (generalists) made a diagnosis on both the needle and open biopsy specimens. Afterwards, three pathologists and two radiologists with extensive experience in breast pathology (experts) diagnosed all of the biopsy specimens. The general pathologists made a similar histological diagnosis as the experts in 632 (88%) of the needle biopsies and 649 (90%) of the open biopsy specimens. Accordingly, the interobserver agreement for the diagnosis of large-core needle biopsies between the general and experts pathologists was excellent (kappa 0.83) and not significantly different from the interobserver agreement for the diagnosis of open breast biopsies (kappa 0.86). However, many inconsistencies were observed in the category of borderline lesions: only 24% of the large-core needle biopsies and 43% of the open biopsies with an expert diagnosis of 'borderline' were diagnosed similarly by the general pathologists. Additionally, the risk of benign/malignant inconsistencies between general pathologists and experts was approximately 1 in 55 for both needle and open biopsies.

Background: For the evaluation of nonpalpable lesions of the breast, image-guided 14-gauge automated needle biopsy is increasingly replacing wire-localized excision. When ductal carcinoma-in-situ (DCIS) is diagnosed at core biopsy, invasive cancer is found in approximately 17% of excision specimens. These so-called DCIS underestimates pose a problem for patients and surgeons, because they generally cause extension of treatment. We evaluated DCIS underestimates in detail to assess reasons for missing the invasive component at core biopsy. This evaluation also included a histological comparison with true DCIS (DCIS at core biopsy and excision)., Methods: Between 1997 and 2000, DCIS was diagnosed at 14-gauge needle biopsy in 255 patients. In 41 cases (16%), invasive cancer was found at excision. We performed a thorough histopathological and radiological review of all these DCIS underestimates, including a histological comparison with core biopsy specimens of 32 true DCIS cases. We assessed the main reason for missing the invasive component at core biopsy., Results: Causes for DCIS underestimates were categorized into "mainly radiological" (n = 20), "mainly histopathological" (n = 15), and "histological disagreements" (n = 6). High-grade DCIS and periductal inflammation in core biopsies made a DCIS underestimate 2.9 and 3.3 times more likely, respectively., Conclusions: A variety of radiological and histopathological reasons contribute to the DCIS underestimate rate. Approximately half of these are potentially avoidable.

We have investigated aromatase and the inducible cyclooxygenase COX-2 expression using immunocytochemistry in tumors of a series of patients with advanced breast cancer treated with aromatase inhibitors. Aromatase was expressed in 58/102 breast cancers. This is similar to the percentage previously reported for aromatase activity. Interestingly, aromatase was expressed in a variety of cell types, including tumor, stromal, adipose, and endothelial cells. Since prostaglandin E2 is known to regulate aromatase gene expression and is the product of COX-2, an enzyme frequently overexpressed in tumors, immunocytochemistry was performed on the tissue sections using a polyclonal antibody to COX-2. Aromatase was strongly correlated (P<0.001) with COX-2 expression. These results suggest that PGE2 produced by COX-2 in the tumor may be important in stimulating estrogen synthesis in the tumor and surrounding tissue. No correlation was observed between aromatase or COX-2 expression and the response of the patients to aromatase inhibitor treatment. However, only 13 patients responded. Nine of these patients were aromatase positive. Although similar to responses in other studies, this low response rate to second line treatment suggests that tumors of most patients were no longer sensitive to the effects of estrogen. Recent clinical studies suggest that greater responses occur when aromatase inhibitors are used as first line treatment. In the intratumoral aromatase mouse model, expression of aromatase in tumors is highly correlated with increased tumor growth. First line treatment with letrozole was effective in all animals treated and was more effective than tamoxifen in suppressing tumor growth. Letrozole was also effective in tumors failing to respond to tamoxifen, consistent with clinical findings. In addition, the duration of response was significantly longer with the aromatase inhibitor than with tamoxifen, suggesting that aromatase inhibitors may offer better control of tumor growth than this antiestrogen.