Frits H. Jansen

Localization of non-palpable breast cancer using a radiolabelled titanium seed.

Resection guided by a radiologically placed hookwire is the most common surgical technique for non‐palpable breast cancer. This technique has several well described disadvantages such as incidental migration, kinking or fracture of the wire, and difficult logistics between the radiology, surgical and nuclear medicine departments. Use of an iodine‐125‐radiolabelled (I‐125) seed for localization of non‐palpable breast tumours could potentially prevent these problems.

Trends in incidence and detection of advanced breast cancer at biennial screening mammography in The Netherlands: a population based study

IntroductionThe aims of this study were to determine trends in the incidence of advanced breast cancer at screening mammography and the potential of screening to reduce it.MethodsWe included a consecutive series of 351,009 screening mammograms of 85,274 women aged 50-75 years, who underwent biennial screening at a Dutch breast screening region in the period 1997-2008. Two screening radiologists reviewed the screening mammograms of all advanced screen detected and advanced interval cancers and determined whether the advanced cancer (tumor > 20 mm and/or lymph node positive tumor) had been visible at a previous screen. Interval cancers were breast cancers diagnosed in women after a negative screening examination (defined as no recommendation for referral) and before any subsequent screen. Patient and tumor characteristics were compared between women with advanced cancer and women with non-advanced cancer, including ductal carcinoma in situ.ResultsA total of 1,771 screen detected cancers and 669 interval cancers were diagnosed in 2,440 women. Rates of advanced cancer remained stable over the 12-year period; the incidence of advanced screen-detected cancers fluctuated between 1.5 - 1.9 per 1,000 screened women (mean 1.6 per 1,000) and of advanced interval cancers between 0.8 - 1.6 per 1,000 screened women (mean 1.2 per 1,000). Of the 570 advanced screen-detected cancers, 106 (18.6%) were detected at initial screening; 265 (46.5%) cancers detected at subsequent screening had been radiologically occult at the previous screening mammogram, 88 (15.4%) had shown a minimal sign, and 111 (19.5%) had been missed. Corresponding figures for advanced interval cancers were 50.9% (216/424), 24.3% (103/424) and 25.1% (105/424), respectively. At multivariate analysis, women with a ≥ 30 months interval between the latest two screens had an increased risk of screen-detected advanced breast cancer (OR 1.63, 95%CI: 1.07-2.48) and hormone replacement therapy increased the risk of advanced disease among interval cancers (OR 3.04, 95%CI: 1.22-7.53).ConclusionWe observed no decline in the risk of advanced breast cancer during 12 years of biennial screening mammography. The majority of these cancers could not have been prevented through earlier detection at screening.

Mammography screening in the Netherlands: delay in the diagnosis of breast cancer after breast cancer screening

In a prospective study we determined the frequency and causes of delay in the diagnosis of breast cancer after suspicious screening mammography. We included all women aged 50–75 years who underwent biennial screening mammography in the southern breast cancer screening region of the Netherlands between 1 January 1996 and 1 January 2002. Clinical data, breast imaging reports, biopsy results and breast surgery reports were collected of all women with a positive screening result with a minimum of 2-year follow-up. Of 153 969 mammographic screening examinations, 1615 (1.05%) were positive screens. Breast cancer was diagnosed in 770 (47.9%) of 1607 women for whom follow-up information was available, yielding a cancer detection rate of 5.0 per 1000 women screened. Breast cancer was diagnosed within 3 months following a positive screen in 722 cases (93.8%). The diagnostic delay was 4–6, 7–12 and 13–24 months, respectively, in 11 (1.4%), 24 (3.1%) and nine (1.2%) patients. In four other patients (0.5%), breast cancer was diagnosed after a repeat positive screen, resulting in a diagnostic delay of 25–27 months. Reasons for a diagnostic delay >3 months were erroneous mammographic interpretation of suspicious lesions as benign or probably benign lesions (33 cases), benign biopsies from a malignant lesion (10), and omission to biopsy or remove a lesion that was suspicious at breast imaging (4) or core biopsy (1). We conclude that there is room for improvement in the workup of patients with a positive screening mammography, as seen from data in this screening region. To improve the workup, we suggest that other breast cancer screening programmes also identify delay in breast cancer diagnosis after a positive screen.

Identification of residual breast tumour localization after neo-adjuvant chemotherapy using a radioactive 125 Iodine seed

INTRODUCTION The use of neo-adjuvant chemotherapy has increased in the treatment of loco-regionally advanced primarily operable breast cancer. As a result of improved neo-adjuvant chemotherapy regimes the number of clinical as well as radiological responses have increased. In case of a complete response it is difficult to identify residual disease and to perform an adequate radical breast-conserving surgery. Therefore localization of the original tumour bed is mandatory. In this study we propose a novel technique with a seed containing radioactive 125 Iodine ((125)I). The (125)I has a half-time of 60 days and is therefore still recognisable with a gamma probe after admittance of several courses of neo-adjuvant chemotherapy. MATERIAL AND METHODS In the period from July 2003 and November 2008, 47 consecutive patients had successful (125)I seed localization of a breast tumour before starting neo-adjuvant chemotherapy. RESULTS The overall clinical response rate to neo-adjuvant chemotherapy was 100%. Complete clinical response occurred in 34 patients, partial clinical response occurred in 13 patients. Complete radiological response occurred in 18 patients, partial radiological response occurred in 29 patients. The initial surgical treatment consisted of breast-conserving surgery for all 47 patients, after a mean of 170 days (range: 70-220) after (125)I seed localization. In 19 patients pathology revealed no residual tumour, 23 patients showed a partial response. Only 3 lumpectomies were irradical. CONCLUSION This study has shown that (125)I seed localization is a novel and highly successful technique in localizing the tumour bed in patients who receive neo-adjuvant chemotherapy for breast cancer leading to a high percentage of radical margins in case of breast-conserving surgery.

Detection of Bilateral Breast Cancer at Biennial Screening Mammography in the Netherlands: A Population-based Study

PURPOSE To determine the incidence of bilateral breast cancer at biennial screening mammography and to assess the sensitivity of screening in the detection of bilateral breast cancer. MATERIALS AND METHODS All women gave written informed consent, and the requirement to obtain review board approval was waived. The authors included all 302,196 screening mammograms obtained in 80,466 women aged 50-75 years in a southern breast screening region of the Netherlands between May 1998 and July 2008. During 2-year follow-up, the authors collected clinical data, breast imaging reports, biopsy results, and breast surgery reports from all patients with screening-detected and interval cancers. Two screening radiologists reviewed the screening and clinical mammograms of all bilateral screening-detected and interval cancers for mammographic abnormalities. The radiologists were initially blinded to each others referral opinion, and discrepant assessments were followed by consensus reading. RESULTS Of all women with screening-detected cancer (n = 1555) or interval cancer (n = 585), 52 (2.4%) had bilateral breast cancer. The sensitivity of screening mammography in the detection of bilateral breast cancer was 19% (10 of 52 women; 95% confidence interval: 8.5%, 29.9%). At blinded review, 18 of the 53 tumors not detected at screening (34%) were considered to be missed, 11 (21%) showed nonspecific minimal signs, and 24 (45%) had been mammographically occult at screening. Five women referred for further analysis experienced a 6-17-month delay in the diagnosis of the second breast cancer; in four of those women, the delay resulted from an incorrect Breast Imaging Reporting and Data System classification at clinical mammography. CONCLUSION The sensitivity of screening mammography in the detection of bilateral breast cancer is disappointingly low. Both screening radiologists and clinical radiologists should pay vigorous attention to the contralateral breast to detect bilateral malignancies without diagnostic delay.

Mammographic changes resulting from benign breast surgery impair breast cancer detection at screening mammography.

PURPOSE To study possible explanations for lower screening performance after previous benign breast surgery. PATIENTS AND METHODS We included a consecutive series of 351,009 screening examinations in 85,274 women, obtained between January 1, 1997 and January 1, 2009. The examinations of women with screen detected cancers (SDC) or interval cancers (IC), diagnosed after previous benign breast surgery, were reviewed by two screening radiologists. They determined the presence and degree of post surgical changes, classified breast density and determined whether mammographic interpretation was hampered by tissue characteristics. They also assessed whether the cancer had already been visible at a previous screen. RESULTS Screening sensitivity was lower in women with prior benign breast surgery than without (63.5% (115/181) versus 73.5% (1643/2236), p=0.004). A total of 115 SDCs and 66 ICs were diagnosed in breasts after previous benign breast surgery. Post surgical mammographic alterations in the breast segment where cancer was diagnosed were more distinct in ICs than in SDCs (p=0.001). Women with post surgical mammographic changes at the location of the breast cancer had an increased interval cancer risk (OR=2.12, 95% confidence interval (CI)=1.05-4.26). Limited mammographic interpretation due to tissue characteristics was mentioned, only in three SDCs and one IC. The proportions of SDCs and ICS that were already visible at a previous screen were comparable for women with and without prior surgery (SDC: 47.5% versus 43.8%, p=0.3, IC: 50.0% versus 48.4%, p=0.8). CONCLUSION Previous benign breast surgery decreases screening sensitivity and this is likely due to postoperative mammographic changes.

Lower sensitivity of screening mammography after previous benign breast surgery.

Few data are available on the effect of previous benign breast surgery on screening mammography accuracy. We determined whether sensitivity of screening mammography and tumor characteristics are different for women with and without previous benign breast surgery. We included a consecutive series of 317,398 screening mammograms of women screened between 1997 and 2008. During 2‐year follow‐up, clinical data, breast imaging, biopsy and surgery reports were collected from women with screen‐detected or interval breast cancers. Screening sensitivity, tumor biology and tumor stages were compared between 168 women with breast cancer and prior ipsilateral benign breast surgery and 2,039 women with breast cancer but without previous ipsilateral, benign breast surgery. The sensitivity of screening mammography was significantly lower for women with prior surgery [64.3% (108/168) versus 73.4% (1,496/2,039), p = 0.01]. The concomitant increased interval cancer risk remained significant after logistic regression adjustment for age and breast density (OR = 1.5, 95% CI: 1.1–2.1). Comparing screen‐detected cancers in women with and without prior breast surgery, no significant differences in estrogen receptor status (p = 0.56), mitotic activity (p = 0.17), proportions of large (T2+) tumors (p = 0.6) or lymph node positive tumors (p = 0.4) were found. Also for interval cancers, no differences were found in estrogen receptor status (p = 0.41), mitotic activity (p = 0.39), proportions of large tumors (p = 0.9) and lymph node positive tumors (p = 0.5) between women with and without prior breast surgery. We conclude that sensitivity of screening mammography is significantly lower in women with previous benign breast surgery than without, but tumor characteristics are comparable both for screen detected cancers and interval cancers.

Two-view versus single-view mammography at subsequent screening in a region of the Dutch breast screening programme.

We retrospectively determined the effect of analogue two-view mammography versus single-view mammography at subsequent screens on breast cancer detection and determined financial consequences for a current digital mammography setting. Two screening radiologists reviewed the mammograms of 536 screen detected cancers (SDCs) and 171 interval cancers (ICs) with single-view mammography (medio-lateral-oblique view) at the last but one screen (SDCs) or latest screen (ICs). They determined whether two-view mammography at the last (but one) screen could have increased the cancer detection rate at that screening round. For subsequent screens, the radiologists also assessed the percentage of SDCs and ICs that had been missed at previous two-view screening mammography (SDC) or latest two-view screening (IC), respectively. Additional personnel and digital storage costs for standard two-view mammography at subsequent screening were calculated for digital screening. Two-view mammography could have facilitated earlier cancer detection in 40.9% (219/536) of SDCs and 39.8% (68/171) of ICs. For two-view screens, 24.4% of SDCs (213/871) were missed at previous two-view screening and 29.3% of ICs (110/375) were missed at the latest screen. Overall costs increase € 1.03/screen after implementation of digital two-view mammography. Standard two-view mammography at subsequent screening may modestly increase cancer detection at an earlier stage, whereas additional screening costs are limited.

Trends in breast biopsies for abnormalities detected at screening mammography: a population-based study in the Netherlands

Background:Diagnostic surgical breast biopsies have several disadvantages, therefore, they should be used with hesitation. We determined time trends in types of breast biopsies for the workup of abnormalities detected at screening mammography. We also examined diagnostic delays.Methods:In a Dutch breast cancer screening region 6230 women were referred for an abnormal screening mammogram between 1 January 1997 and 1 January 2011. During two year follow-up clinical data, breast imaging-, biopsy-, surgery- and pathology-reports were collected of these women. Furthermore, breast cancers diagnosed >3 months after referral (delays) were examined, this included review of mammograms and pathology specimens to determine the cause of the delays.Results:In 41.1% (1997–1998) and in 44.8% (2009–2010) of referred women imaging was sufficient for making the diagnosis (P<0.0001). Fine-needle aspiration cytology decreased from 12.7% (1997–1998) to 4.7% (2009–2010) (P<0.0001), percutaneous core-needle biopsies (CBs) increased from 8.0 to 49.1% (P<0.0001) and surgical biopsies decreased from 37.8 to 1.4% (P<0.0001). Delays in breast cancer diagnosis decreased from 6.7 to 1.8% (P=0.003).Conclusion:The use of diagnostic surgical breast biopsies has decreased substantially. They have mostly been replaced by percutaneous CBs and this replacement did not result in an increase of diagnostic delays.

Trends in surgery for screen‐detected and interval breast cancers in a national screening programme

This population‐based study aimed to evaluate trends in surgical approach for screen‐detected cancer versus interval breast cancer, and to determine the factors associated with positive resection margins.