High-risk Breast Lesions Research Articles

Current management of lesions associated with an increased risk of breast cancer.

High-risk breast lesions, which comprise benign lesions and in situ carcinomas (lobular carcinoma in situ and ductal carcinoma in situ), are clinically, morphologically, and biologically heterogeneous and are associated with an increased risk of invasive breast cancer development, albeit to varying degrees. Recognition and proactive management of such lesions can help to prevent progression to invasive disease, and might, therefore, reduce breast cancer incidence, morbidity, and mortality. However, this opportunity comes with the possibility of overdiagnosis and overtreatment, necessitating risk-based intervention. Notably, despite the progress in defining the molecular changes associated with carcinogenesis, alterations identifying the individuals with high-risk lesions that will progress to invasive carcinoma remain to be identified. Thus, until reproducible clinicopathological or molecular features predicting an individual's risk of breast cancer are found, management strategies must be defined by population-level risks as determined by models such as the Gail or IBIS models, as well as patient attitudes toward the risks and benefits of interventions. Herein, we review the contemporary approaches to diagnosis and management of high-risk breast lesions. Progress in this area will ultimately be dependent on the ability to individualize risk prediction through better definition of the key drivers in the carcinogenic process.

A pure mucocele-like lesion of the breast diagnosed on ultrasonography-guided core-needle biopsy: is imaging follow-up sufficient?

Purpose:To evaluate the upgrade rate of ultrasonography (US)-guided core-needle biopsy (CNB) of the breast for a pure mucocele-like lesion (MLL), to evaluate the clinical and radiologic features, and to correlate the image-pathologic features further on to guide the management of MLL.Methods:Between January 2003 and February 2013, 14-gauge US-guided CNB was performed in 18,111 cases. Thirty-two cases associated with MLL were identified, and five cases of MLLs associated with breast carcinoma or with other high-risk breast lesions (i.e., atypical ductal hyperplasia [ADH], papillary lesions, lobular carcinoma in situ, and radial scar complex) were excluded. Among these 27 pure MLLs, 21 cases with surgical or vacuum-assisted excision (VAE) pathology were included in our study. Medical records, mammograms, and ultrasonograms were reviewed for the clinical and radiologic features of the cases.Results:Among the 21 cases with pure MLLs at CNB, the final pathology showed a 0% proportion of cases upgraded to malignancy. All the 21 cases with either surgical or VAE pathology were benign MLLs including three cases of focal involvement of ADH (14.3%). The common features were mammographic features of microcalcifications that were round in shape and had a grouped distribution. The US features included oval shape, circumscribed margin, parallel orientation, complex solid and cystic echo pattern, no posterior feature, and complex solid and cystic echoic masses. The predominant Breast Imaging Reporting and Data System (BIRADS) category was 4A. All the lesions showed image-pathologic concordance.Conclusion:For pure MLL on US-guided CNB with image-pathologic concordance, close imaging follow-up might be considered instead of surgical excision.

Efficacy of second-time vacuum-assisted breast excision in the management of screen-detected high-risk breast lesions

Surgical excision of breast lesions is usually required for high-risk (B3) lesions or radiological pathological discordance. The risk of underestimation of malignancy is 45 to 50% for 14G core biopsy and 20 to 25% for vacuum-assisted biopsies (VAB).

Abstract 4105: Prevalence of breast stem cells in high-risk benign breast lesions and association with breastfeeding

Abstract Background: Invasive breast cancers contain a subpopulation of cancer stem cells that are thought to maintain the heterogeneity and self-renewing potential of the tumor. In our previously published data, we demonstrated that stem cells in normal adjacent tissues were associated with triple negative breast cancer. The objective of this study is to determine the presence of stem cells in high risk breast lesions. We hypothesized that stem cells in high-risk lesions and normal adjacent breast tissue may represent a biomarker for increased breast cancer risk. Methods: We identified biopsies from 42 high-risk women seen in the Cancer Prevention Center at The University of Texas MD Anderson Cancer Center between 1988-2011. We collected information on breast cancer risk factors. The biopsies contained high-risk lesions including ductal carcinoma in situ (DCIS) n=21, lobular carcinoma in situ (LCIS) n=5, atypical ductal hyperplasia (ADH) n=7 and atypical lobular hyperplasia (ALH) n=6. The tissues were fluorescently labeled for stem cell markers CD44/CD49f/CD133, and were scored positive if more then 1% cells were positive for all markers using an automated fluorescent microscopy software. The presence of stem cell markers was compared in the normal adjacent tissues and high-risk lesions from a subset of 25 patients. Results: We identified stem cells in 46% of samples containing DCIS, 67% of LCIS, 63% of ALH, and 70% of ADH. There was a 79% concordance in stem cell positive status between the high-risk lesion and adjacent normal tissue. Women with positive stem cell high-risk lesions had no significant difference in age at first birth (24.4 years vs 26.6 years p=0.3), parity (1.7 vs 1.9, p=0.5), or body mass index (27.8 vs 31.8, p=0.07) compared to women without positive stem cell high-risk lesions. Women with positive stem cell high-risk lesions had shorter breastfeeding duration than women without (2.4 months vs 9.0 months p= 0.05). Conclusion: This is the first report, to our knowledge, that stem cells are present in some high-risk lesions and their associated normal breast tissue. Correlation with future development of invasive breast cancer could lay the foundation for future targeted breast cancer prevention strategies. Citation Format: Rachel L. Atkinson, Fraser Symmans, Therese B. Bevers, Wendy A. Woodward, Abenaa M. Brewster. Prevalence of breast stem cells in high-risk benign breast lesions and association with breastfeeding. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4105. doi:10.1158/1538-7445.AM2014-4105

A multivariate model to predict cancer upgrade from atypical ductal hyperplasia by core needle biopsy.

3 Background: Atypical ductal hyperplasia (ADH) is a high-risk breast lesion usually diagnosed with core needle biopsy. Although upgraded to cancer at surgical excision in ~15 to 25% of cases, routine excision is questioned due to cost and overtreatment. We evaluated clinical, imaging, and histologic features associated with cancer upgrade and developed a multivariate model to predict risk of upgrade. Methods: With IRB approval a single institution retrospective review was performed of patients who underwent surgical excision of ADH diagnosed by core biopsy from 06/2005 to 06/2013. Review was performed of electronic records, breast imagin,g and biopsy slides. Multiple imputations were used for missing data. Association of cancer upgrade with various features was assessed with logistic regression. Results: 409 biopsies with ADH on core biopsy, with later surgical excision, were included. The overall upgrade rate was (16.1%, 95% CI:12.9-20.0%); 10 patients had invasive cancer at excision and 56 DCIS only. Features on core biopsy most strongly associated with upgrade were imaging estimated percent of lesion removed (upgrade 9% for 90% removed, 14% for 50 to 75%, and 27% for < 50% removed), individual cell necrosis (upgrade 34% with necrosis vs. 9.5% without), and # foci of ADH (22% for >1 focus vs 8% for 1 focus). A multivariate predictive model (see Table) showed an average C-statistic of 0.77. Women with no necrosis and either 1 focus with ≥ 50% removal or >1 focus with 90% removal (36% of the sample) have low risk of upgrade (5.0%, 95% CI:1.3-8.7%). Conclusions: ADH on core biopsy with low risk of upgrade to cancer is defined by percent of imaging lesion removed, # of foci of ADH, and lack of individual cell necrosis. If findings are validated, women whose biopsies meet low-risk criteria might be considered for chemoprevention and surveillance rather than surgical excision.[Table: see text]

Quelle prise en charge chirurgicale pour « les lésions à haut risque » de cancer du sein ?

Diagnostics of high-risk breast lesions have increased these last years with the augmentation of breast percutaneous biopsies. They are lesions that confer an enlarged risk of breast cancer, either because of an increased probability of finding cancer after open surgery, a possible evolution toward in situ or invasive cancer, or because of an increased probability of developing breast cancer over the long term. Much progress has been made these last years in their histological diagnostic, classification and pathogenesis. Nevertheless, no consensus exists to date on the management of these “high-risk” lesions. In particular, surgical indications and follow-up modalities remain controversial for each histological type. In this review, the principal factors that could impact surgical decision and long-term follow-up are discussed with areas of controversy highlighted.

Prediction of near-term risk of developing breast cancer using computerized features from bilateral mammograms

Asymmetry of bilateral mammographic tissue density and patterns is a potentially strong indicator of having or developing breast abnormalities or early cancers. The purpose of this study is to design and test the global asymmetry features from bilateral mammograms to predict the near-term risk of women developing detectable high risk breast lesions or cancer in the next sequential screening mammography examination. The image dataset includes mammograms acquired from 90 women who underwent routine screening examinations, all interpreted as negative and not recalled by the radiologists during the original screening procedures. A computerized breast cancer risk analysis scheme using four image processing modules, including image preprocessing, suspicious region segmentation, image feature extraction, and classification was designed to detect and compute image feature asymmetry between the left and right breasts imaged on the mammograms. The highest computed area under curve (AUC) is 0.754±0.024 when applying the new computerized aided diagnosis (CAD) scheme to our testing dataset. The positive predictive value and the negative predictive value were 0.58 and 0.80, respectively.

Abstract P5-01-09: Early tumor antigens discovered in TgMMTV-neu mice may provide targets for early breast cancer diagnosis and prevention

Abstract Breast cancer is immunogenic and breast tumor proteins stimulate both an antibody and a T cell immune response. Identification of cancer related proteins that become immunogenic prior to the clinical development of cancer may allow the use of humoral immunity to identify those “exposed” to the cancer phenotype. Alternatively, these proteins that become aberrant enough to trigger such early immune recognition may be ideal targets for a vaccine aimed at preventing the development of breast cancer. We used the TgMMTV-neu mouse model to discover immunogenic proteins i.e. proteins expressed in pre-invasive breast cancer. The mammary tumors in these mice are genotypically similar to human luminal breast cancer and can be evaluated longitudinally, allowing for collection of pre-diagnostic sera prior to tumor development to use for antigen discovery. We identified 6 antigens that were present in mice prior to the development of mammary cancer (Pdhx, Otud6b, Stk39, Zpf238, Lgals8, and Vps35). These proteins were associated with inflammation, autoimmunity, and cellular homeostasis. In mouse validation cohorts, detecting IgM and IgG antibody responses against a panel of three “pre-diagnostic” tumor antigens discriminated pre-diagnostic sera from non-transgenic control sera with an AUC of 0.924. We next evaluated samples obtained from the Women's Health Initiative Study and demonstrated women with autoantibodies to the human homologues of these proteins. IgM and IgG autoantibodies to the “pre-diagnostic” antigen panel could discriminate the samples of women who eventually developed breast cancer from matched controls. The discriminatory potential of the pre-diagnostic autoantibodies was enhanced if samples were collected more than 5 months prior to diagnosis (AUC 0.68; CI 0.565-0.787). We questioned whether these antigens, which could predict women who would eventually develop breast cancer, could mediate anti-tumor immunity. When TgMMTV-neu mice (n = 5/group) were vaccinated with the individual antigens, vaccination with Pdhx inhibited tumor growth by 62.1%, Otud6B inhibited tumor growth by 23.5%, and Stk39 inhibited tumor growth by 50.3% as compared to empty vector vaccinated control at 27 weeks (p<0.001 for each of the individual antigens as compared to empty vector). Spontaneous tumorigenesis was inhibited in TgMMTV-neu mice (n = 20 mice/group) vaccinated with a panel of three of the “pre-diagnostic” antigens (Pdhx, Otud6b, and Stk39) inhibited tumor growth by 27.3% by 37 weeks as compared to vector vaccinated mice (p<0.05). These data suggest that the same pre-invasive breast tumor proteins are found in mice and women and vaccines against these pre-invasive breast cancer proteins inhibit tumorigenesis in mice, future studies will address if these antigens elicit T-cell responses in patients with high risk breast lesions. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-01-09.

Does Digital Mammography Increase Detection of High-Risk Breast Lesions Presenting as Calcifications?

The objective of our study was to evaluate whether the transition from film-screen mammography (FSM) to digital mammography (DM) was associated with increased detection of high-risk breast lesions. A retrospective search identified 142 cases of atypia or lobular neoplasia (LN) diagnosed in women with mammographic calcifications between January 2004 and August 2010. We excluded lesions upgraded to cancer at excisional biopsy, lesions in women with ipsilateral cancer within 2 years of mammography, and lesions that presented as a mass only. The cases included in the cohort were 82 (57.7%) cases of atypical ductal hyperplasia; 17 (12%) atypical lobular hyperplasia; 25 (17.6%) lobular carcinoma in situ (LCIS); 12 (8.5%) atypia and LCIS; and six (4.2%) other atypia. The institution transitioned from predominantly performing FSM in 2004 to performing only DM by 2010. Pathology was interpreted by breast pathologists. The annual detection rate was calculated by dividing the number of high-risk lesions by mammography volume. Of the 142 cases of atypia or LN, 52 (36.6%) were detected using FSM and 90 (63.4%) were detected using DM. The detection rate was higher with DM (1.24/1000 mammographic studies) than FSM (0.37/1000 mammographic studies). The detection rate by year ranged between 0.21 and 0.64 per 1000 mammographic studies for FSM and between 0.32 and 1.49 per 1000 mammographic studies for DM. The median size of the calcifications was 8 mm on DM and 7 mm on FSM. The most common appearance was clustered amorphous or indistinct calcifications on both FSM and DM. The transition from FSM to DM was associated with a threefold increase in the detection rate of high-risk lesions. Improved detection may allow enhanced screening, risk reduction treatment, and possibly breast cancer prevention. However, increased detection of high-risk lesions may also result in oversurveillance and treatment.

Upgrade of high-risk breast lesions detected on mammography in the Breast Cancer Surveillance Consortium

BackgroundUpgrade rates of high-risk breast lesions after screening mammography were examined. MethodsThe Breast Cancer Surveillance Consortium registry was used to identify all Breast Imaging Reporting and Data System category 4 assessments followed by needle biopsies with high-risk lesions. Follow-up was performed for all women. ResultsHigh-risk lesions were found in 957 needle biopsies, with excision documented in 53%. Most (n = 685) were atypical ductal hyperplasia (ADH), 173 were lobular neoplasia, and 99 were papillary lesions. Upgrade to cancer varied with type of lesion (18% in ADH, 10% in lobular neoplasia, and 2% in papillary lesions). In premenopausal women with ADH, upgrade was associated with family history. Cancers associated with ADH were mostly (82%) ductal carcinoma in situ, and those associated with lobular neoplasia were mostly (56%) invasive. During a further 2 years of follow-up, cancer was documented in 1% of women with follow-up surgery and in 3% with no surgery. ConclusionsDespite low rates of surgery, low rates of cancer were documented during follow-up. Benign papillary lesions diagnosed on Breast Imaging Reporting and Data System category 4 mammograms among asymptomatic women do not justify surgical excision.

Abstract P4-13-03: Hormone replacement therapy, is there an increased risk of in situ breast cancer ? data from a french cohort

Abstract Background: Use of hormone replacement therapy (HRT) has been associated with an increased risk of breast cancer. Few studies focus on correlation between HRT and in situ breast cancer A large cohort study, the Million Women Study (Reeves GK et al. Lancet Oncol. 2006) have shown that the use of HRT has been associated with an increased incidence of in situ breast cancer (RR = 1, 55, IC=1, 4–1,72, p = 0,03). Purpose: We investigated the association between HRT use and duration and in situ breast cancer incidence from a data base of infraclinic breast lesions. Materials & Methods: From 2007 to 2011, 2708 patients (pts) with a non palpable breast lesion were referred to our breast disease unit for exploration (Saint Louis Hospital, Paris). Radiological abnormalities were screened by mammography and/or breast ultrasound, and/or MRI. Out of 2708 pts, 1668 had a biopsy. All biopsies were seen by an anatomopathologist dedicated to breast. Here, we focus on the 1017 postmenopausal women (61%). Results: Biopsies revaled invasive breast cancers in 222 pts (22%), in situ breast cancers in 164 pts (16%) [10 lobular in situ carcinoma and 154 ductal in situ carcinoma], high risk breast lesions in 103 pts (10%) and benign breast lesions in 528 patients (52%). Characteristics of the 164 patients with in situ breast cancer: median age 62 [IQR: 57 to 68], at least one pregnancy (mean number of pregnancies per woman, 1.6) 75,6%, family history of breast cancer:30,2%. Among these 164 patients, 42.6 % had used an oral contraceptive and 53% of them a HRT, with a mean duration of use of 7 years. The HRT use was not significantly associated with in situ breast cancer (p = 0.66) as well as the duration of HRT. Discussion: In this study of postmenopausal women, HRT use, whatever is the duration, was not associated with in situ breast cancer. Although a lack of statistical power may be invoked to explain these results, these findings suggest that the type of the HRT could be important to explain the difference between our study and the Million Women Study. In our study, the HRT used is in the majority of the pts, percutaneous oestrogens and natural progesterone as it is the most commun HRT used in France (Fournier A, Int J Cancer. 2005) during this period of time. Use and type of HRT are different in USA where conjugated estrogens and medroxy progestogerone acetate were commonly used. Conclusion: We therefore encourage further studies to better appreciate the links between type of HRTs and in situ breast cancer. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-13-03.

Pure Flat Epithelial Atypia (FEA) on Sterotactic Biopsies Performed In Clinica Alemana de Santiago

FOREWORD: Flat Epithelial Atypia (FEA) is one of the high-risk breast lesions (HRL), with low degree cytological atypia. Its management (surgery v/s intensive follow-up) after percutaneous procedures diagnosis is still controversial. OBJECTIVES: The goal of the study was to determine the frequency of pure FEA on stereotactic biopsies (SB) and the histological underestimation (HU) after it s surgical excision. MATERIALS AND METHODS: Retrospective review of 537 SB performed in 485 women (30-72 yr), old (mean 49.9 yr. ) in Clinica Alemana de Santiago between June 2009 and April 2012. To assess HU, were excluded cases with other high-risk lesions (atypical ductal hyperplasia, lobular neoplasia, radial scar, mucocelelike lesions, papillary lesions) and ductal carcinoma in situ (DCIS) or invasive cancer in the SB histology. Also excluded pure FEA cases that didn t undergo surgical excision. RESULTS: Of all biopsied focuses, 217 (40.4%) were high risk lesions, and FEA was found on 175 of them (80.6%). Pure FEA was diagnosed in 38 cases (7% total; 17.5% HRL); of such 20 (52.6%) underwent surgical excision. (i) No cases with DCIS or invasive cancer (UH 0%) was found in the definitive histology.(ii) 40 % of FEA cases were associated to atypical ductal hyperplasia and 20% to lobular neoplasia. From the 18 patients did not undergo surgery, 10 (55.5%) continued to be monitored, with a mean follow-up of 14 month. Only one case showed progression of residual micro-calcifications, and was suggested to biopsy again. CONCLUSION: FEA is a diagnosis to by familiar with, especially because of lack of enough scientific evidence that allows to create handling patterns after is diagnosed by percutaneal procedures. Our results suggest that surgery may not be needed in all cases, especially when FEA appears as a collateral finding, or unique focus, microfocus or when a full extraction of micro-calcifications during biopsy is achieved.

A program to increase use of chemoprevention for women with high-risk breast lesions.

46 Background: Tamoxifen, raloxifene, and exemestane have been demonstrated to reduce risk of breast cancer in high-risk women, bututilization is very low.Among the reasons cited are lack of awareness and reluctance of physicians to prescribe. Women with high-risk breast lesions are generally candidates for chemoprevention and can be evaluated and counseled in a high-risk breast clinic. Knowledge about drugs that can prevent breast cancer may increase uptake among high-risk women. Methods: In a single practice, women with a diagnosis of atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), lobular carcinoma in situ (LCIS), or severe atypical ductal hyperplasia/borderline ductal carcinoma in situ are offered an extended visit with a nurse practitioner in the Breast and Ovarian Cancer Risk and Prevention Clinic. The visit includes data collection, patient interview about relevant history and personal preferences, risk assessment, including use of relevant models (via HughesRiskApps.com), and recommendations for surveillance and prevention. Emphasis is placed on understanding of individual risk as well as risks and benefits and appropriateness of chemoprevention and surveillance modalities. Based on personal and family history, women are advised if chemoprevention is appropriate to consider, their choice is made, and they are encouraged to have surveillance in the Breast Clinic. Results: Since January 2001, 487 women with a diagnosis of ADH, ALH or LCIS, or severe ADH have been evaluated and counseled in the Breast and Ovarian Cancer Risk and Prevention Clinic. 132/487 (27%) were advised against taking chemoprevention and 355/487 (73%) were appropriate for chemoprevention. Of those for whom chemoprevention was clinically appropriate, 188/355 (53%) took one of the medications, or participated in a chemoprevention trial. 53/188 (28%) did not complete therapy (discontinued at 2 weeks to 54 months) due to preference or side effects. 75 women have completed five years of therapy and 60 are currently on therapy. Conclusions: When provided with personalized information about breast cancer risk and the pros and cons of chemoprevention, many women will choose to take medication to reduce breast cancer risk.

Does atypical ductal hyperplasia require 6 months of postoperative surveillance?

60 Background: Standard follow-up imaging for women with a history of breast cancer is well defined, but the appropriate screening guidelines for other high risk breast lesions, such as atypical ductal hyperplasia (ADH), remain unclear. Current practices often parallel those of cancer patients and include a 6 month interval mammogram prior to resuming annual screening, which may be unnecessary. As such, it is critical to evaluate the utility of the current standard practice of additional screening beyond a routine annual mammogram. Methods: Our pathology database was queried for the phrase "atypical ductal hyperplasia" from 2008 to 2010, and patients who underwent surgical excision were identified. Those who did not have subsequent follow up at our institution were excluded. Results: There were 44 patients who underwent excisional biopsies that were diagnosed with ADH and proceeded with follow up. In addition to a routine clinical exam, a short-term follow up diagnostic mammogram was performed in 24 patients. The median age was 56.5 years, and the median breast cancer risk assessment scores were 2.8% at 5 years and 13.4% lifetime. Of the 24 interval mammograms, 21 yielded benign findings on initial imaging (BIRADS 2), while 3 patients (12.5%) required additional imaging that ultimately resulted in benign findings. There were only 4 patients with a lifetime risk ≥25%, and all of these patients had benign findings on their initial imaging and resumed routine follow up. To date, 22 patients have received at least one additional mammogram, and all subsequent findings have been benign. No additional biopsies or surgeries have been performed. Conclusions: In sum, a clinical exam is still recommended at 6 months following surgical excision for a diagnosis of ADH. In the post-surgical breast, imaging may be misleading and result in psychological distress for patients and possibly unnecessary procedures. Based on our findings, a 6-month follow up mammogram is not recommended and patients should resume annual surveillance.

High-Risk Breast Lesions at Imaging-Guided Needle Biopsy: Usefulness of MRI for Treatment Decision

The purpose of this study is to evaluate the role of MRI for characterization of high-risk breast lesions diagnosed at imaging-guided needle biopsy. In this retrospective analysis of 220 patients, 227 high-risk lesions (94 papillomas, 64 radial sclerosing lesions, 46 lobular neoplasias, and 23 atypical ductal hyperplasias) found at 11-gauge vacuum-assisted or 14-gauge needle biopsy were studied with dynamic MRI (time resolution, 84 or 88 seconds; gadopentetate dimeglumine or gadobenate dimeglumine, 0.1 mmol/kg). When lesions showed contrast enhancement on subtracted images, they were considered suspicious for malignancy. The reference standard was histopathologic examination after surgical excision in 190 of 227 (84%) lesions and negative follow-up (≥ 24 months) in 37 of 227 (16%) lesions. Predictive values and likelihood ratios were calculated. Of 227 lesions, 155 (68%) were contrast enhancing and 72 (32%) were not. Of 155 contrast-enhancing lesions, 28 (18%) were upgraded to malignancy after surgical excision (nine papillomas, one radial sclerosing lesion, 11 lobular neoplasias, and seven atypical ductal hyperplasias); there were 11 invasive carcinomas and 17 ductal carcinomas in situ, four of the latter being G3. Of 72 non-contrast-enhancing lesions, two (3%) were upgraded to malignancy after surgical excision (one radial sclerosing lesion and one lobular neoplasia), both of which were G1 ductal carcinoma in situ. Cancer probability was significantly higher for contrast-enhancing (18%) than for non-contrast-enhancing (3%) lesions (p = 0.001) and for nonmasslike (43%) than for masslike (14%) lesions (p = 0.005). The positive predictive value was 18% (28/155; 95% CI, 13-24%), the negative predictive value was 97% (70/72; 95% CI, 94-99%), the positive likelihood ratio was 1.448 (95% CI, 1.172-1.788), and the negative likelihood ratio was 0.188 (95% CI, 0.152-0.232). The absence of enhancement at dynamic MRI allowed reliable exclusion of invasive cancers among high-risk lesions diagnosed at needle biopsy.

Breast-specific Gamma Imaging in the Detection of Atypical Ductal Hyperplasia and Lobular Neoplasia

Atypical lesions such as atypical ductal hyperplasia (ADH) and lobular neoplasia are nonmalignant lesions that are associated with significant increased risk of developing breast cancer. Atypical lesions have been reported to present with focal increased radiotracer uptake on breast-specific gamma imaging (BSGI) examination, a novel physiologic tool for the detection of breast cancer. To date the sensitivity of BSGI in the detection of atypical lesions has not been reported. The purpose of this study is to determine the sensitivity of BSGI in detecting ADH and lobular neoplasia. A total of 1316 patients who received a BSGI exam between January 2006 and July 2009 were retrospectively reviewed. All patients who underwent minimally invasive biopsy and subsequent surgical excision where the highest pathology was solely ADH or lobular neoplasia (reported as ALH, lobular carcinoma in situ or lobular neoplasia), according to the pathology database were included (n = 15). The sensitivity was determined as the percentage of positive BSGI exams out of all patients diagnosed with ADH or lobular neoplasia who received a BSGI. Patient ages ranged from 39 to 67 (mean, 52). Eight of 15 patients had ADH, 6/15 lobular neoplasia, and 1/15 ADH and lobular neoplasia in one lesion. Fifteen of the 15 (100%) patients with surgically confirmed ADH or lobular neoplasia had a positive BSGI, with focally increased radiotracer uptake at the site of the verified high-risk lesion. BSGI has a high sensitivity for the detection of atypical, high-risk breast lesions. A diagnosis of an atypical lesion is concordant with focal increased radiotracer uptake with BSGI and can identify women at increased risk for breast cancer.

Evaluation of Molecular Breast Imaging in Women Undergoing Myocardial Perfusion Imaging with Tc-99m Sestamibi

Our objective was to explore the potential benefits of molecular breast imaging (MBI) as a screening technique in women undergoing stress myocardial perfusion studies. MBI was offered to women receiving Tc-99m sestamibi injection for myocardial perfusion stress testing. During the required waiting period after stress isotope injection, MBI was performed using a dedicated breast imaging gamma camera system. MBI examinations were interpreted by breast radiologists, with review of a recent mammogram in cases with positive MBI. Of 322 women enrolled, 313 completed MBI, comprising 5 with known breast cancer, 2 with known high-risk benign breast lesions, and 306 who were asymptomatic for breast disease with a recent negative mammogram. Analysis was limited to the 306 patients with no known breast disease. MBI was positive in 22 of 306, giving a recall rate of 7.2% (95% confidence interval [CI] 4.8-10.6]. MBI detected 4 new cancers, resulting in a supplemental diagnostic yield of 13.1/1000 women screened (95% CI 5.1-33.2). The number of cancers diagnosed per abnormal MBI examinations (PPV(1)) was 18% (4 of 22) (95% CI 7.3-38.5), and the number diagnosed per MBI-prompted biopsies (PPV(3)) was 44% (4 of 9) (95% CI 18.9-73.3). The addition of MBI to clinically indicated stress myocardial perfusion imaging studies in women results in a high diagnostic yield of newly detected breast cancers while generating a low rate of additional unnecessary workup.

Multidisciplinary Considerations in the Management of High-Risk Breast Lesions

The purpose of this review is to discuss the controversy and lack of consensus in the management of high-risk breast lesions, including flat epithelial atypia, atypical ductal hyperplasia, lobular neoplasia, radial scar, papillary lesions, and mucocelelike lesions, after diagnosis with core needle biopsy. A single uniform approach may not be appropriate for the management of all high-risk breast lesions. A multidisciplinary team may offer individualized treatment options for patients.

P4-10-09: Hormone Replacement Therapy: A Benign Breast Disease's Risk?

Abstract Background Use of hormone replacement therapy (HRT) has been associated with increased risk of breast cancer. However relations between use of HRT and benign breast lesions remain contradictory (1-3). Our goal was to investigate whether HRT and its duration use are associated with benign breast lesions. Materials & Methods From 2001 to 2007, 2708 patients with a non palpable breast lesion were referred to our breast care center. Radiological abnormalities were screened either by breast ultrasound mammography, or MRI. Of those, 1 329 patients had a biopsy in our Radiology Unit. We focus on the postmenopausal women (n=739). Clinical data including HRT use extent were reported. Patients with previous history of benign breast disease or malignancy were excluded. Results The analysis was performed on 739 patients. Biopsies yielded a benign result in 414 (56%) of them (fibroadenoma n=71, blunt duct adenosis n=94, fibrocystic disease n=92, epithelial hyperplasia n=56, others n=101), high risk lesions in 57 (8%) (atypical ductal hyperplasia n=28, atypical lobular hyperplasia n=19, lobular carcinoma in situ n=10) and malignancy in 268 (36%) (not studied here). For the 471 patients with benign or high risk breast lesion, the median age was 59 years, 80% had at least one pregnancy and 27% had a family history of breast cancer. Among these 471 patients, 47% of them had used an oral contraceptive and 53% of them a HRT, with a mean duration of use of 2 years. The HRT use was not significantly associated with the type of benign or high risk breast disease. No association was observed either between breast disease and duration of HRT (less or more than 7 years respectively).Older age was significantly correlated to atypia or carcinoma (median age at diagnosis 59 y.o in benign lesions, 60 y.o in high risk lesions and 62 y.o in malign lesions, with significant difference) (p<0,0001). Conclusion In this study of postmenopausal women, HRT and its duration use were not associated with the type of benign or high risk breast lesion. Although a lack of statistical power may be invoked to explain the results, we are called to believe that the magnitude of an effect of HRT use is small, if ever it exists. 1. Finkelde DT, Kitchen PR, Hayes PR, McKinlay MR, Henderson MA 2001 Symptomatic benign breast disease and hormone replacement therapy. Breast 10:127–130 2. Gayet A, Esteve J, Seradour B, Piana L, Jacquemier J 2003 Does hormone replacement therapy increase the frequency of breast atypical hyperplasia in postmenopausal women? Results from the Bouches du Rhone district screening campaign. Eur J Cancer 39:1738–1745 3. Rohan TE, Miller AB 1999 Hormone replacement therapy and risk of benign proliferative epithelial disorders of the breast. Eur J Cancer Prev 8:123–130 Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-10-09.

Effect of infertility treatment and pregnancy-related hormones on breast cell proliferation in vitro

Breast cancer development involves a series of mutations in a heterogeneous group of proto-oncogenes/tumor suppressor genes that alter mammary cells to create a microenvironment permissive to tumorigenesis. Exposure to hormones during infertility treatment may have a mutagenic effect on normal mammary epithelial cells, high-risk breast lesions and early-stage breast cancers. Our goal was to understand the association between infertility treatment and normal and cancerous breast cell proliferation. MCF-10A normal mammary cells and the breast cancer cell lines MCF-7 [estrogen receptor (ER)-positive, well differentiated] and HCC 1937 (ER-negative, aggressive, BRCA1 mutation) were treated with the weak ER activator clomiphene citrate and hormones that are increased during infertility treatment. Direct effects of treatment on cell proliferation and colony growth were determined. While clomiphene citrate had no effect on MCF-10A cells or MCF-7 breast cancer cells, it decreased proliferation of HCC 1937 versus untreated cells (P= 0.003). Estrogen had no effect on either MCF-10A or HCC 1937 cells but, as expected, increased cell proliferation (20-100 nM; P≤0.002) and colony growth (10-30 nM; P< 0.0001) of MCF-7 cells versus control. Conversely, progesterone decreased both proliferation (P= 0.001) and colony growth (P= 0.01) of MCF-10A cells, inhibited colony size of MCF-7 cells (P= 0.01) and decreased proliferation of HCC 1937 cells (P= 0.008) versus control. hCG (100 mIU/ml) decreased both proliferation (P ≤ 0.01) and colony growth (P ≤ 0.002) of all three cell lines. Although these data are preclinical, they support possible indirect estrogenic effects of infertility regimens on ER-positive breast cancer cells and validate the potential protective effect of pregnancy-related exposure to hCG.