Preoperative axillary imaging with percutaneous lymph node biopsy is valuable in the contemporary management of patients with breast cancer.

BACKGROUND: ACOSOG Z11 and other studies showing little benefit to axillary dissection (ALND) for early-stage breast cancers with limited nodal disease have led to questioning the value of preoperative axillary imaging ± ultrasound-guided needle biopsy (USNB). Data are lacking on the value of this approach in identifying cases that fall outside Z11 guidelines. METHODS: We studied 988 consecutive patients with invasive breast cancers who underwent operation including axillary surgery in 2010-2011. RESULTS: Preoperative axillary ultrasonography (AUS) was performed in 92% and breast/axillary magnetic resonance imaging (MRI) in 51%; 82 (33.5%) of 245 patients with suspicious lymph nodes (LN) were USNB-positive. Regarding nodal status, AUS, MRI, and USNB had negative and positive predictive values of 78%, 76%, 70% and 54%, 58%, 100%, respectively. AUS/MRI visualization of one versus multiple abnormal LNs visualized predicted >2LN+ on final pathology (13.5%/15.1% % vs 30.8%/32.6%, P < .009). Among USNB-LN+ T1/T2 patients, 51.6% had 1-2 LN+ while 60% with multiple and 31% with one AUS-abnormal LN(s) had > 2LN+, P = .001. CONCLUSION: In our contemporary series, preoperative AUS±USNB streamlined surgical care for 29% of node-positive patients. Two-thirds of T1/T2 USNB-LN+ patients with multiple AUS-suspicious LNs had >2LN+, suggesting they should undergo ALND without SLNB. AUS±USNB helps identify node-positive breast cancer patients who fall outside Z11 guidelines.

Invasive micropapillary carcinoma of the breast: imaging features with clinical and pathologic correlation.

OBJECTIVE: The purpose of this article is to present imaging findings of invasive ductal carcinoma with micropapillary features with clinical and pathologic correlation. MATERIALS AND METHODS: We retrospectively searched our institution's surgical pathology database for patients with pathologically proven invasive ductal carcinoma with micropapillary features. Forty-one patients with images available for review were included in the study. Mammographic, sonographic, and MRI findings were assessed using the American College of Radiology's BI-RADS lexicon. Molecular breast imaging findings were reviewed using a molecular breast imaging lexicon. Imaging findings were correlated with clinical presentation and pathologic findings. RESULTS: Mammographically, the most common finding was an irregular spiculated mass. Sonographically, the most common finding was an irregular hypoechoic mass with spiculated margins and posterior acoustic shadowing. With MRI, the most common finding was an irregular mass with washout kinetics, but we also observed diffuse heterogeneous nonmasslike enhancement throughout the breast. Molecular breast imaging was available for one patient and showed multicentric radiotracer uptake. Analysis of 39 pathologic specimens showed 27 (69%) with angiolymphatic invasion. Axillary nodal metastases were present in 23 patients (59%), nine (23%) with extranodal extension. CONCLUSION: The imaging features of invasive ductal carcinoma of the breast with micropapillary features typically were highly suggestive of malignancy. The malignancies were strongly associated with lymphovascular invasion and lymph node metastases. Radiologists should be aware of the imaging features of this unusual variant and should consider axillary sonography if this entity is found in a core needle biopsy specimen.

CYP2D6 metabolism and patient outcome in the Austrian Breast and Colorectal Cancer Study Group trial (ABCSG) 8.

PURPOSE: Controversy exists about CYP2D6 genotype and tamoxifen efficacy. EXPERIMENTAL DESIGN: A matched case-control study was conducted using the Austrian Breast and Colorectal Cancer Study Group Trial 8 (ABCSG8) that randomized postmenopausal women with estrogen receptor (ER)-positive breast cancer to tamoxifen for 5 years (arm A) or tamoxifen for 2 years followed by anastrozole for 3 years (arm B). Cases had disease recurrence, contralateral breast cancer, second non-breast cancer, or died. For each case, controls were identified from the same treatment arm of similar age, surgery/radiation, and tumor-node-metastasis (TNM) stage. Genotyping was conducted for alleles associated with no (PM; *3, *4, *6), reduced (IM; *10, and *41), and extensive (EM: absence of these alleles) CYP2D6 metabolism. RESULTS: The common CYP2D6*4 allele was in Hardy-Weinberg equilibrium. In arm A during the first 5 years of therapy, women with two poor alleles [PM/PM: OR, 2.45; 95% confidence interval (CI), 1.05-5.73, P = 0.04] and women with one poor allele (PM/IM or PM/EM: OR, 1.67; 95% CI, 0.95-2.93; P = 0.07) had a higher likelihood of an event than women with two extensive alleles (EM/EM). In years 3 to 5 when patients remained on tamoxifen (arm A) or switched to anastrozole (arm B), PM/PM tended toward a higher likelihood of a disease event relative to EM/EM (OR, 2.40; 95% CI, 0.86-6.66; P = 0.09) among women on arm A but not among women on arm B (OR, 0.28; 95% CI, 0.03-2.30). CONCLUSION: In ABCSG8, the negative effects of reduced CYP2D6 metabolism were observed only during the period of tamoxifen administration and not after switching to anastrozole.

p16(INK4a) expression and breast cancer risk in women with atypical hyperplasia.

p16, a nuclear protein encoded by the p16(INK4a) gene, is a regulator of cell-cycle regulation. Previous studies have shown that expression of p16 in tissue biopsies of patients with ductal carcinoma in situ (DCIS) is associated with increased risk of breast cancer, particularly when considered in combination with other markers such as Ki-67 and COX-2. Here, we evaluated how expression of p16 in breast tissue biopsies of women with atypical hyperplasia (AH), a putative precursor lesion to DCIS, is associated with subsequent development of cancer. p16 expression was assessed by immunohistochemistry in archival sections from 233 women with AH diagnosed at the Mayo Clinic. p16 expression in the atypical lesions was scored by percentage of positive cells and intensity of staining. We also studied coexpression of p16, with Ki-67 and COX-2, biomarkers of progression in AH. Risk factor and follow-up data were obtained via study questionnaire and medical records. Forty-seven patients (20%) developed breast cancer with a median follow-up of 14.5 years. Staining of p16 was increased in older patients relative to younger patients (P = 0.0025). Although risk of developing breast cancer was not associated with increased p16 expression, joint overexpression of Ki-67 and COX-2 was found to convey stronger risk of breast cancer in the first 10 years after diagnosis as compared with one negative marker (P < 0.01). However, the addition of p16 levels did not strengthen this association. p16 overexpression, either alone or in combination with COX-2 and Ki-67, does not significantly stratify breast cancer risk in women with AH.

Collision tumors with synchronous presentation of breast carcinoma and lymphoproliferative disorders in the axillary nodes of patients with newly diagnosed breast cancer: a case series.

Although occurrence of a second tumor is a well-recognized phenomenon in patients with a treated malignancy, simultaneous presentation with a second primary malignancy ("collision tumor") is rare in patients with breast cancer. We report a series of 7 patients who were undergoing axillary nodal staging of a newly diagnosed breast cancer. Six patients were found to have collision tumors in their axillary lymph nodes consisting of metastatic breast cancer and a previously unknown lymphoproliferative disorder. In 1 additional patient, a lymph node biopsy of a palpable axillary node resulted in the diagnosis of metastatic breast cancer and lymphoma. Awareness and diagnosis of such collision tumors will lead to appropriate management of each malignancy.

Evaluation of the Tyrer-Cuzick (International Breast Cancer Intervention Study) model for breast cancer risk prediction in women with atypical hyperplasia.

PURPOSE: Accurate breast cancer risk assessment is vital to personalize screening and risk reduction strategies. Women with atypical hyperplasia have a four-fold higher risk of breast cancer. We evaluated the performance of the Tyrer-Cuzick model, which was designed to predict 10-year risk of breast cancer development, in a well-defined cohort of women with atypia. PATIENTS AND METHODS: The Mayo Benign Breast Disease cohort includes 9,376 women who had a benign breast biopsy between 1967 and 1991. Among those, 331 women with atypia were identified by our study pathologists. Risk factor data for the Tyrer-Cuzick model were collated for each woman and used to predict individual risk of developing invasive breast cancer within 10 years. RESULTS: Over a median follow-up of 14.6 years, 64 (19%) of the 331 women developed invasive breast cancer. In the first 10 years after biopsy, 31 women developed invasive breast cancer whereas the Tyrer-Cuzick model predicted 58.9. The observed-to-predicted ratio was 0.53 (95% CI, 0.37 to 0.75). The concordance statistic was 0.540, revealing that the Tyrer-Cuzick model did not accurately distinguish, on an individual level, between women who developed invasive breast cancer and those who did not. CONCLUSION: The Tyrer-Cuzick model significantly overestimated risk of breast cancer for women with atypia, and individual risk estimates showed poor concordance between predicted risk and invasive breast cancer development. Thus, we cannot recommend the use of the Tyrer-Cuzick model to predict 10-year breast cancer risk in women with atypical hyperplasia.

Predicting four or more metastatic axillary lymph nodes in patients with sentinel node-positive breast cancer: assessment of existent risk scores.

BACKGROUND: Patients with metastases in four or more axillary lymph nodes (≥4+ALN) represent a subset of patients with breast cancer who are at increased risk of local recurrence and who benefit from postmastectomy radiation. Risk prediction models designed to identify such patients have been published by Rivers et al., Chagpar et al., and Katz et al. We sought to evaluate and compare the performance of these models in an independent patient population. METHODS: We reviewed 454 patients with breast cancer with one to three positive sentinel lymph nodes who underwent completion axillary lymph node dissection at our institution. Each of the three published models was applied to our sample as described in the respective publications. The models' performances were analyzed with the Hosmer-Lemeshow goodness-of-fit test and with the area under the curve (AUC). Sensitivity, specificity, and false-negative percentages were calculated for clinically meaningful cutoff points of each score. RESULTS: Of 454 eligible patients, 87 (19.2%) had four or more positive axillary nodes. The Rivers, Chagpar, and Katz models demonstrated good calibration in our population based on the Hosmer-Lemeshow test (p = 0.82, p = 0.73, p = 0.71, respectively). Assessment of discriminatory ability for the models resulted in AUCs of 0.81, 0.73, and 0.81, respectively. CONCLUSIONS: The Rivers and Katz models performed well in our patient population and may be clinically useful to predict patients with ≥4+ALN. However, their clinical utility is limited by the current controversy surrounding the use of postmastectomy radiation for all node-positive patients.

Primary and secondary angiosarcoma of the breast: the Mayo Clinic experience.

BACKGROUND AND OBJECTIVES: Angiosarcoma of the breast can be divided into primary and secondary. The objective was to determine clinicopathologic factors associated with breast angiosarcoma and to compare primary versus secondary angiosarcoma. METHODS: Breast angiosarcoma cases at Mayo Clinic from 1960 to 2008 were identified. Clinicopathologic factors were reviewed. Characteristics of primary and secondary angiosarcoma were compared. RESULTS: Twenty-seven cases of primary angiosarcoma and 14 cases of secondary angiosarcoma were identified. The median age of primary angiosarcoma patients was lower than that of secondary angiosarcoma--43 years versus 73 years (P < 0.0001). Primary angiosarcoma more frequently presented with a mass, whereas secondary angiosarcoma presented with a rash (P < 0.0001). Median time from radiation to secondary angiosarcoma diagnosis was 6.8 years. Median tumor size was 7.0 cm for primary angiosarcoma and 5.0 cm for secondary angiosarcoma (P = 0.7). Tumors were high grade in 33% of primary angiosarcoma and 82% of secondary angiosarcoma (P = 0.02). Five-year survival for primary and secondary angiosarcoma was 46% and 69%, respectively (P = 0.8). CONCLUSION: Primary angiosarcoma occurs in younger patients than secondary and more frequently presents with a mass. Mastectomy is the mainstay of treatment for breast angiosarcoma. Breast angiosarcoma is a rare malignancy with poor long-term prognosis.

Impact of American Society of Clinical Oncology/College of American Pathologists guideline recommendations on HER2 interpretation in breast cancer.

Accurate assessment of human epidermal growth factor receptor 2 is critical for the management of patients with breast cancer. We set out to study the impact of the 2007 American Society of Clinical Oncology/College of American Pathologists guidelines on the interpretation of human epidermal growth factor receptor 2 IHC results and its correlation with fluorescence in situ hybridization results. Invasive breast carcinomas with IHC HercepTest 3+ were retrieved from the archive of Mayo Clinic Rochester. The human epidermal growth factor receptor 2 slides were rereviewed, and results were recorded as percentage of invasive tumor cells with 3+, 2+, 1+, and 0 staining intensity. Human epidermal growth factor receptor 2 gene amplification by fluorescence in situ hybridization was performed on all tumors with 3+ staining in 70% or less of tumor cells. Of the 141 cases studied, 12 cases showed intense membrane staining in 11% to 30% of the invasive tumor cells and would have been scored as 2+ according to the new American Society of Clinical Oncology/College of American Pathologists guidelines. Of these 12 cases, 6 were positive for human epidermal growth factor receptor 2 gene amplification by fluorescence in situ hybridization (ratio >2.2), 4 cases were negative (HER2/CEP17 ratio of < 1.8), and 2 cases were equivocal (ratio of 1.8-2.2). One human epidermal growth factor receptor 2-positive case showed dramatic intratumoral heterogeneity with high-level amplification (ratio of 12.2) in the IHC 3+ area and no amplification (ratio of 1.0) in the IHC 1+/2+ areas. The 2007 American Society of Clinical Oncology/College of American Pathologists guidelines down-scored 2.8% of tumors from human epidermal growth factor receptor 2-positive (IHC 3+) to human epidermal growth factor receptor 2-negative (IHC 2+ equivocal and fluorescence in situ hybridization negative) in this study. Clinical studies are needed to determine whether the updated guidelines are better at predicting response to anti-human epidermal growth factor receptor 2 therapy.

Sentinel lymph node surgery for staging of breast carcinoma in patients with lymphoproliferative disease.

There are few reports confirming the validity of sentinel lymph biopsy in patients with a background of lymphoproliferative disease. We reviewed nine cases of women who underwent sentinel lymph node (SLN) surgery for staging of primary breast cancer with a diagnosis of lymphoproliferative disease. SLN identification rate was 100 per cent with a background of lymphoma in the sentinel node in eight of the nine patients. With a mean follow-up of 37 months, there have been no axillary recurrences in any of these patients. These cases illustrate that SLN staging is feasible and provides axillary staging information in women with breast cancer despite synchronous lymphoproliferative disease.

Automated cellular imaging system III for assessing HER2 status in breast cancer specimens: development of a standardized scoring method that correlates with FISH.

The goal of this study was to assess the performance characteristics of the Automated Cellular Imaging System (ACIS III) for HER2 immunohistochemical analysis. The study was performed on 187 biopsy slides from patients who underwent HER2 testing between January and February 2008. Three scoring methods by the ACIS III were compared with the manual score and fluorescence in situ hybridization (FISH) results for HER2 amplification. The equal distribution score (EQD) method, in which 2 areas each of high-, moderate-, and low-intensity staining were measured, most closely matched the FISH HER2 amplification result. The numbers of immunohistochemically negative (0 or 1+)/FISH+ cases were equivalent for all methods. The EQD method had significantly fewer 2+ cases (n = 16) (P < .001) vs the manual method (n = 35) and yielded a higher positive predictive value (38%) for HER2 amplification compared with the manual method (20%). The EQD method may more accurately identify FISH-amplified HER2 cases with fewer 2+ cases that would be "reflexed" to FISH compared with the manual method.

Novel breast tissue feature strongly associated with risk of breast cancer.

PURPOSE: Accurate, individualized risk prediction for breast cancer is lacking. Tissue-based features may help to stratify women into different risk levels. Breast lobules are the anatomic sites of origin of breast cancer. As women age, these lobular structures should regress, which results in reduced breast cancer risk. However, this does not occur in all women. METHODS: We have quantified the extent of lobule regression on a benign breast biopsy in 85 patients who developed breast cancer and 142 age-matched controls from the Mayo Benign Breast Disease Cohort, by determining number of acini per lobule and lobular area. We also calculated Gail model 5-year predicted risks for these women. RESULTS: There is a step-wise increase in breast cancer risk with increasing numbers of acini per lobule (P = .0004). Adjusting for Gail model score, parity, histology, and family history did not attenuate this association. Lobular area was similarly associated with risk. The Gail model estimates were associated with risk of breast cancer (P = .03). We examined the individual accuracy of these measures using the concordance (c) statistic. The Gail model c statistic was 0.60 (95% CI, 0.50 to 0.70); the acinar count c statistic was 0.65 (95% CI, 0.54 to 0.75). Combining acinar count and lobular area, the c statistic was 0.68 (95% CI, 0.58 to 0.78). Adding the Gail model to these measures did not improve the c statistic. CONCLUSION: Novel, tissue-based features that reflect the status of a woman's normal breast lobules are associated with breast cancer risk. These features may offer a novel strategy for risk prediction.

Mammary fibromatosis.

OBJECTIVE: This article illustrates the imaging findings that have pathologic correlation and the clinical presentation of mammary fibromatosis. CONCLUSION: Mammary fibromatosis is a rare, benign, nonmetastasizing stromal tumor. It presents clinically and radiologically as a palpable, spiculated, and locally invasive tumor that is suspicious for malignancy. MRI is ideal for evaluation of chest wall involvement. Although histologically benign, the tumor is locally aggressive and has significant recurrence rates. On occasion, recurrence may require radical surgery.

Lobular involution: localized phenomenon or field effect?

As women age, the lobules in their breasts undergo involution. We have shown that, in women with benign breast disease, progressive involution assessed near the benign lesion is associated with lower breast cancer risk. However, it is unknown whether the extent of involution is variable or uniform across the entire breast. We compared involution across the four quadrants of both breasts for fifteen women undergoing bilateral prophylactic mastectomy. One pathologist classified involution extent as none (0% involuted lobules), mild (1-24%), moderate (25-74%), or complete (> or =75%). We assessed intra-woman concordance using intraclass correlation coefficients (ICCs), kappa coefficients, and pairwise comparisons of agreement. We found strong intra-woman concordance of involution across the eight quadrants of breast tissue (ICC = 0.75, 95% CI 0.59, 0.89). Our study suggests that lobular involution is a homogeneous process, supporting the use of involution measures from a single benign biopsy as a component in breast cancer risk assessment paradigms.

Cytochrome P450 2D6 and homeobox 13/interleukin-17B receptor: combining inherited and tumor gene markers for prediction of tamoxifen resistance.

PURPOSE: Genetic variation in cytochrome P450 2D6 (CYP2D6) and the gene expression ratio of the homeobox 13 (HOXB13) to interleukin-17B receptor (IL17BR) are associated with tamoxifen resistance. We sought to determine the combined effect of inherited (CYP2D6) and somatic (HOXB13/IL17BR) gene variation in tamoxifen-treated breast cancer. EXPERIMENTAL DESIGN: Retrospective analysis of women with node-negative breast cancer randomized to receive 5 years of tamoxifen (North Central Cancer Treatment Group 89-30-52). CYP2D6 metabolism (extensive or decreased) was based on CYP2D6*4 genotype and presence/absence of a CYP2D6 inhibitor. Reverse transcription-PCR profiles for HOXB13 and IL17BR and the cut point separating patients into high- and low-risk categories according to disease-free survival (DFS) were used. A risk factor (CYP2D6:HOXB13/IL17BR) representing the four categories of combining CYP2D6 metabolism (extensive or decreased) and HOXB13/IL17BR (low or high) was created. The association between CYP2D6:HOXB13/IL17BR and DFS and overall survival (OS) was assessed using the log-rank test and proportional hazards modeling. RESULTS: CYP2D6 metabolism and HOXB13/IL17BR gene ratio was available in 110 of 160 (69%) patients. The combined CYP2D6:HOXB13/IL17BR risk factor was significantly associated with DFS (log-rank P = 0.004) and OS (P = 0.009). Relative to women with extensive CYP2D6 metabolism and low HOXB13/IL17BR, those with either decreased metabolism or a high HOXB13/IL17BR ratio had significantly worse OS (adjusted hazard ratio, 2.41; 95% confidence interval, 1.08-5.37; P = 0.031), whereas women with both decreased metabolism and high HOXB13/IL17BR ratio had the shortest survival (adjusted hazard ratio, 3.15; 95% CI, 1.17-8.52; P = 0.024). CONCLUSIONS: An index composed of inherited (CYP2D6) and tumor (HOXB13/IL17BR) gene variation identifies patients with varying degrees of resistance to tamoxifen.

Molecular analysis of metaplastic breast carcinoma: high EGFR copy number via aneusomy.

Metaplastic breast carcinoma, a rare tumor composed of adenocarcinomatous and nonglandular growth patterns, is characterized by a propensity for distant metastases and resistance to standard anticancer therapies. We sought confirmation that this tumor is a basal-like breast cancer, expressing epidermal growth factor receptor (EGFR) and stem cell factor receptor (KIT). EGFR activating mutations and high copy number (associated with response to tyrosine kinase inhibitor gefitinib) and KIT activating mutations (associated with imatinib sensitivity) were then investigated. Seventy-seven metaplastic cases were identified (1976-2006); 38 with tumor blocks available underwent pathologic confirmation before EGFR and KIT immunohistochemical analyses. A tissue microarray of malignant glandular and metaplastic elements was constructed and analyzed immunohistochemically for cytokeratin 5/6, estrogen receptor, progesterone receptor, and p63, and by fluorescence in situ hybridization for EGFR and HER-2/neu. DNA isolated from individual elements was assessed for EGFR and KIT activating mutations. All assessable cases were negative for estrogen receptor, progesterone receptor, and (except one) HER2. The majority were positive for cytokeratin 5/6 (58%), p63 (59%), and EGFR overexpression (66%); 24% were KIT positive. No EGFR or KIT activating mutations were present; 26% of the primary metaplastic breast carcinomas were fluorescence in situ hybridization-positive, displaying high EGFR copy number secondary to aneusomy (22%) and amplification (4%). We report here that metaplastic breast carcinoma is a basal-like breast cancer lacking EGFR and KIT activating mutations but exhibiting high EGFR copy number (primarily via aneusomy), suggesting that EGFR tyrosine kinase inhibitors should be evaluated in this molecular subset of breast carcinomas.

Sentinel node positive breast cancer patients who do not undergo axillary dissection: are they different?

BACKGROUND: Little data address outcome in patients with sentinel lymph node (SN) metastases without completion axillary lymph node dissection (CALND). This study was designed to assess locoregional recurrence in patients with positive SNs who did not undergo CALND. METHODS: An IRB-approved, retrospective chart review was conducted on breast cancer patients with a positive SN. Follow-up information on outcomes was obtained via mailed questionnaires and chart review. Comparative analyses were performed between patients who did and did not undergo CALND after a positive sentinel lymph node biopsy. RESULTS: From November 1998 to June 2004, 625 breast cancer patients had a positive sentinel lymph node biopsy. One-hundred and eighteen patients with < or = 0.2 mm nodal metastases (N0i+) were excluded from the study. Of the remaining 507 patients, 421 underwent CALND and 86 did not. In comparison to patients who had CALND, patients who did not undergo CALND had smaller primary tumors (2 vs 2.6 cm, P = .0007) and were more likely to have a single positive sentinel node (92% vs 77%, P = .002). The metastasis size of the sentinel node was smaller compared to patients who underwent axillary dissection (1.7 vs 6.4 mm, P < .0001). Mean predicted probability of nonsentinel node metastasis in patients who did not undergo CALND was 20% compared to 47% in patients who did (P < .0001). During a median follow-up of 30 months, there were no axillary recurrences. CONCLUSIONS: These data confirm that patients who have a positive sentinel node biopsy and do not undergo CALND have a lower risk profile for axillary disease. In this lower risk subset, axillary treatment may not be necessary.

Breast cancer risk in women with radial scars in benign breast biopsies.

BACKGROUND: The risk for subsequent breast cancer in women diagnosed with radial scar lesions (RS) on benign breast biopsy remains controversial. We studied the relative risk of radial scar lesions in a large cohort of patients with benign breast disease (BBD). METHODS: Radial scars were identified in a BBD cohort of 9,262 patients biopsied at Mayo Clinic between 1967 and 1991. Radial scar lesions were classified as proliferative disease without atypia (PDWA) unless atypia was present (classified as atypical hyperplasia [AH]). The observed number of breast cancers developing among those with RS was compared to that expected in the general population using standardized incidence ratios (SIRs, mean follow-up interval 17 years). RESULTS: RS were identified in 439 (4.7%) of the cohort members; 382 (87.0%) contained one RS, 42 (9.6%) contained two, 9 (2.0%) contained three, and 6 (1.4%) contained four or more. The majority of RS (356, 82.4%) were less than 5.0 mm in diameter; 60 (13.9%) were 5.0-9.9 mm, and 16 (3.7%) were 10.0 mm or greater. The relative risk for women with PDWA and RS was 1.88 (95% CI, 1.36-2.53), no different than PDWA without RS [relative risk 1.57 (95% CI, 1.37-1.79) (P=0.29)]. Women with atypical hyperplasia and RS (n=60) had a relative risk of 2.81 (95% CI, 1.29-5.35), while those with atypia but without RS had a relative risk of 3.97 (95% CI, 2.99-5.19). CONCLUSIONS: RS imparts no increased breast cancer risk above that of PDWA or AH without RS.

A multidisciplinary approach to the management of breast cancer, part 2: therapeutic considerations.

New approaches to breast cancer treatment have enhanced clinical outcomes and patient care. These approaches include advances in breast irradiation and hormonal and systemic adjuvant therapies. In addition to the identification of new drug targets and targeted therapeutics (eg, trastuzumab), there is renewed re-emphasis in the development of biomarkers for the prediction of response to therapy. One example is the pharmacogenetics of tamoxifen metabolism and the individualization of hormonal therapy. The current treatment of breast cancer continues to evolve rapidly, with new scientific and clinical achievements constantly changing the standard of care and leading to substantial reductions in breast cancer mortality. The goal of this article is to provide clinicians who care for women with breast cancer a multidisciplinary, state-of-the art approach to the treatment of these patients.

A multidisciplinary approach to the management of breast cancer, part 1: prevention and diagnosis.

Breast cancer is the most common cancer among women in the United States, with an estimated 200,000 new cases diagnosed annually. A multidisciplinary focus that entails prevention, diagnosis, and treatment has led to significant strides in the reduction of breast cancer incidence and mortality. Additionally, breast cancer management has become increasingly complex, requiring comprehensive assessment and review of multiple issues that include the role of genetic testing, imaging and breast magnetic resonance imaging, surgical and reconstructive options, and a variety of new adjuvant therapies. It has become more evident that a multidisciplinary team approach that involves a spectrum of breast experts is necessary to provide optimal care to patients. This team includes medical oncologists, breast radiologists, breast pathologists, surgical breast specialists, radiation oncologists, geneticists, and primary care physicians. Furthermore, patient knowledge has increased use of the Internet, and more patients are seeking a multidisciplinary approach to treatment. This review considers information for health care professionals who will facilitate optimal patient care for women at increased risk for or presenting with a new diagnosis of breast cancer. The multidisciplinary team of authors, representing the different disciplines, has selected important state-of-the-art issues that arise in their daily practices for consideration, rather than summarizing what is already available in textbooks.