Purpose To compare the effectiveness of mammography, breast ultrasound, and magnetic resonance imaging (MRI) for surveillance of women at increased familial risk for breast cancer (lifetime risk of 20% or more). Patients and Methods We conducted a surveillance cohort study of 529 asymptomatic women who, based on their family history and/or mutational analysis, were suspected or proven to carry a breast cancer susceptibility gene (BRCA). A total of 1,542 annual surveillance rounds were completed with a mean follow-up of 5.3 years. Diagnostic accuracies of the three imaging modalities used alone or in different combinations were compared. Results Forty-three breast cancers were identified in the total cohort (34 invasive, nine ductal carcinoma-in-situ). Overall sensitivity of diagnostic imaging was 93% (40 of 43 breast cancers); overall node-positive rate was 16%, and one interval cancer occurred (one of 43 cancers, or 2%). In the analysis by modality, sensitivity was low for mammography (33%) and ultrasoun...

http://gulfimagingmri.com/PDFs/MammographyUltasoundMRIforHigh-RiskWomen.pdf

Mammography, Breast Ultrasound, and Magnetic Resonance Imaging for Surveillance of Women at High Familial Risk for Breast Cancer

The biological application of nanoparticles is a rapidly developing area of nanotechnology that raises new possibilities in the diagnosis and treatment of human cancers. In cancer diagnostics, fluorescent nanoparticles can be used for multiplex simultaneous profiling of tumour biomarkers and for detection of multiple genes and matrix RNA with fluorescent in-situ hybridisation. In breast cancer, three crucial biomarkers can be detected and accurately quantified in single tumour sections by use of nanoparticles conjugated to antibodies. In the near future, the use of conjugated nanoparticles will allow at least ten cancer-related proteins to be detected on tiny tumour sections, providing a new method of analysing the proteome of an individual tumour. Supermagnetic nanoparticles have exciting possibilities as contrast agents for cancer detection in vivo, and for monitoring the response to treatment. Several chemotherapy agents are available as nanoparticle formulations, and have at least equivalent efficacy and fewer toxic effects compared with conventional formulations. Ultimately, the use of nanoparticles will allow simultaneous tumour targeting and drug delivery in a unique manner. In this review, we give an overview of the use of clinically applicable nanoparticles in oncology, with particular focus on the diagnosis and treatment of breast cancer.

https://www.thelancet.com/pdfs/journals/lanonc/PIIS1470-2045(06)70793-8.pdf

Emerging use of nanoparticles in diagnosis and treatment of breast cancer.

Women at high risk for breast cancer need a highly sensitive screening test. This review summarizes data from 11 prospective studies that screened very high-risk women with mammography plus magneti...

Systematic review: using magnetic resonance imaging to screen women at high risk for breast cancer.

Magnetic resonance (MR) imaging is emerging as the most sensitive modality that is currently available for the detection of primary or recurrent breast cancer. Although this technique has been shown to be an extremely powerful diagnostic tool, it is still relatively rarely used in clinical practice, as compared with other applications of MR imaging such as for musculoskeletal or brain and spine imaging. This is the second of a two-part series on the current status of breast MR. Part two provides an overview of the use of breast MR imaging in clinical patient care, the body of evidence that supports its use. A discussion is provided on the many controversies that exist regarding breast MR imaging for preoperative staging and for screening.

Current status of breast MR imaging. Part 2. Clinical applications.

This review supports the U.S. Preventive Services Task Force recommendations on genetic counseling and BRCA testing for susceptibility to breast and ovarian cancer.

Genetic risk assessment and BRCA mutation testing for breast and ovarian cancer susceptibility: systematic evidence review for the U.S. Preventive Services Task Force.

BACKGROUND

At present, there is no consensus regarding how frequently BRCA mutation carriers should be screened for malignancies using breast imaging techniques. An interval malignancy is defined as a malignancy that becomes evident during the period between annual screening mammography scans; the finding of such a malignancy indicates that the malignancy either went undetected by the last breast imaging scan or developed during the interval since that last scan.



METHODS

The authors retrospectively reviewed the medical charts of all BRCA mutation carriers who were followed by the genetic counselor at the Columbia-Presbyterian Comprehensive Breast Center (New York, NY) between September 1995 and September 2002.



RESULTS

Thirteen BRCA mutation carriers elected to undergo close surveillance and thus were followed at our institution. Three of these 13 patients (23%) did not develop breast carcinoma, 4 (31%) developed breast carcinoma that was detected at the time of annual screening, and 6 (46%) developed palpable interval malignancies in less than 12 months. Among the six patients who developed interval malignancies, the mean time between the last screening mammogram and disease presentation was 5.1 months (range, 2–9 months); the average tumor size in this patient subgroup was 1.7 cm (range, 0.8–3 cm). Two of these six patients had ductal carcinoma in situ, whereas the remaining four had invasive breast carcinoma; three patients had positive lymph nodes at presentation. All six patients who developed interval disease exhibited dense breast tissue on the previous mammogram. Focused breast ultrasonography was able to identify the tumor mass in 3 of 4 patients (75%).



CONCLUSIONS

Nearly half of all BRCA-positive women who chose to undergo close surveillance in the current study developed malignant disease less than a year after exhibiting normal findings on screening mammography. Half of these interval malignancies were positive for lymph node involvement. These results suggest that strong consideration should be given to screening BRCA-positive women at more frequent intervals and to using additional imaging techniques, such as breast ultrasonography and/or breast magnetic resonance imaging, as a part of this screening. Cancer 2004. © 2004 American Cancer Society.

The development of interval breast malignancies in patients with BRCA mutations

Background The lack of a standard definition of “pure” mucinous carcinoma of the breast has made it difficult to compare data from different studies. This study used the most stringent criteria to define parameters for truly pure lesions. Methods Sixty-five patients were identified. The database was used to evaluate patients' demographics, tumor characteristics, and outcomes. Survival curves and predictors of survival were analyzed. Results The mean age of presentation was 67 years. The majority (96%) of patients presented with early-stage disease. The 5- and 10-year overall survival rates were 93.6% and 72.8%, respectively. The number of involved axillary lymph nodes was the only significant predictor of death ( P = 0.02). Conclusions Pure mucinous carcinoma of the breast has a favorable prognosis. Tumor size does not appear to impact survival, perhaps because the volume of mucin overestimates tumor burden. The number of involved axillary lymph nodes was the only significant predictor of death from disease.

Pure mucinous carcinoma of the breast

Background: Genetic mutation is responsible for approximately 10% of breast cancers. The purpose of this study was to compare breast cancer survival and recurrence rates between BRCA1/2 mutation carriers and noncarriers. Methods: Using the Columbia Presbyterian breast cancer database, we collected the tissue blocks of all patients younger than 65 years of age and of Jewish descent. The patients were contacted and the data updated. DNA was extracted from the tissue blocks and tested for the common mutations. The results of the genetic mutation and updated database were anonymized and merged. The survival and recurrence rates were compared between mutation carriers and noncarriers. Results: A total of 739 breast cancer cases in 715 patients were identified. We were able to test 487 patients. We identified 30 BRCA1 and 21 BRCA2 mutation carriers, for an incidence of 10.36%. The median follow-up for the patients tested was 50 months. BRCA1 patients more frequently had estrogen- and progesterone-negative tumors and had a higher incidence of positive nodes. BRCA1 patients received chemotherapy more frequently. The incidence of in situ disease was similar for mutation and non–mutation carriers. BRCA1/2 mutation carriers had a higher incidence of bilateral disease. There was no difference in 5- or 10-year overall and breast cancer–specific survival between mutation and non–mutation carriers. Conclusions: Breast cancer patients with BRCA1/2 mutations have a similar outcome as non–mutation carriers.

Survival and recurrence after breast cancer in BRCA1/2 mutation carriers.

Background The purpose of this study was to determine the utility of breast-imaging studies in identifying cancer and high-risk lesions among patients with spontaneous, single-duct, nipple discharge (SSND) Methods The medical records of 168 cases with SSND treated with duct excision between June 1998 and May 2004 were reviewed The sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) of mammogram, ultrasound, and ductogram in predicting high-risk lesions and cancer were calculated Results The sensitivity of mammography was 10%, the specificity 94%, the NPV 88%, and the PPV 18% Ultrasongraphy had a sensitivity of 36%, specificity of 68%, PPV of 14%, and NPV of 89% Ductography had a sensitivity of 75%, specificity of 49%, and NPV and PPV of 93% and 18%, respectively Conclusions Conventional imaging studies do not accurately identify cancer or high-risk lesions in patients with SSNDAll patients with SSND should be offered duct excision

The value of clinical characteristics and breast-imaging studies in predicting a histopathologic diagnosis of cancer or high-risk lesion in patients with spontaneous nipple discharge.

Meier curves demonstrated that there was no significant difference in overall survival. The 5- and 10-year survivals for women were 0.77 and 0.51, and for men 0.77 and 0.56. When the Kaplan-Meier curves for breast cancer– specific survival were compared, however, there was a significant difference in the 5- and 10-year survivals (P=.05, log-rank test). For women, the 5- and 10-year disease-specific survival was 0.81 and 0.7, respectively, while for men it was 0.9 and 0.9, respectively. In a Cox regression analysis for time to death from breast cancer, stagewastheonlypredictorofdeaththatapproachedsignificance (P=.06). Conclusions: While the overall survivals were equivalent, male breast cancer patients had significantly better disease-specific survivals compared with their female counterparts. Male patients were 4 times more likely to die of other causes than their breast cancer.

https://jamanetwork.com/journals/jamasurgery/articlepdf/770297/soa3240_1079_1082.pdf

Beth-Ann Ditkoff

Papers

The development of interval breast malignancies in patients with BRCA mutations

Pure mucinous carcinoma of the breast

Survival and recurrence after breast cancer in BRCA1/2 mutation carriers.

The value of clinical characteristics and breast-imaging studies in predicting a histopathologic diagnosis of cancer or high-risk lesion in patients with spontaneous nipple discharge.

Men with breast cancer have better disease-specific survival than women.