Radiation Oncology/Breast/Benign

By analogy to colon CA, breast lesions may develop in a linear fashion:
 * Normal -> Usual ductal hyperplasia -> Atypical ductal hyperplasia -> DCIS -> Invasive CA
 * Causal evidence is lacking


 * Mayo, 2005 (1967-1991) PMID 16034008 -- "Benign breast disease and the risk of breast cancer." (Hartmann LC, N Engl J Med. 2005 Jul 21;353(3):229-37.)
 * Retrospective. 9087 women with benign breast disease, compared to SEER registry. Median F/U 15 years
 * Histology: Nonproliferative 67%, proliferative without atypia 30%, atypical hyperplasia 4%
 * Relative risk: overall 1.6; nonproliferative 1.3 (but if also no FH, RR 1.0); proliferative without atypia 1.9, atypical hyperplasia 4.2
 * Family history independent risk factor

Radial Scar

 * Region of central sclerosis, surrounded by epithelial proliferative lesions, cystic changes, and papillomas extending radially from the central sclerosis. If >1.0 cm, can be termed "complex sclerosing lesions"
 * On screening mammogram, may be indistinguishable from small invasive CA
 * It appears to be pertuberation of normal stroma, but whether it is a precursor lesion is yet to be established
 * Associated with invasive/DCIS pathology ~20%, proliferative/ADH pathology ~20%, and benign ~60%
 * One study (Nurses Heatlh Study, 1999) found presence of RS to be an independent risk factor for BCA. However, a larger study (Vanderbilt, 2006) found that the risk is largely attributable to co-existent proliferative disease (e.g ADH)
 * If there is associated invasive CA, DCIS, or proliferative pathology, it should be managed as such. There is no consensus as yet on how to manage benign solitary radial scar


 * Ottawa, 2006 (1995-2003) PMID 16944680 -- "Management of radial scars found at percutaneous breast biopsy." (Becker L, Can Assoc Radiol J. 2006 Apr;57(2):72-8.)
 * Retrospective. 184/227 radial scar biopsies done via 14-gauge (144 biopsies) or 11-gauge bx (40 biopsy). 30 lesions 14-gauge followed by 11-gauge
 * Presence of RS: associated with CA 20%, high-risk lesion 20%, benign lesion 60%.
 * Specificity: 4% CA missed (5% for 14-gauge and 0% for 11-gauge), underestimated in 22% (25% and 17%).
 * Conclusion: If benign RS found on 14-gauge, need 11-gauge or surgery. If benign RS found on 11-gauge, mammographic follow up sufficient


 * Vanderbilt, 2006 (1950-1986) PMID 16502407 -- "Interdependence of radial scar and proliferative disease with respect to invasive breast carcinoma risk in patients with benign breast biopsies." (Sanders ME, Cancer. 2006 Apr 1;106(7):1453-61.)
 * Retrospective. 9556 women (biopsied) enrolled in Nashville Breast Cohort. RS in 9.2% Most found incidentally. Average F/U 20.4 years
 * Risk of IBC: RS 7.0% vs. 5.5% controls (RR 1.8 at 10 years, SS). 92% of women with RS had proliferative disease; but RS only present in 1.3% of bx without proliferative disease. Stratifying for proliferative disease resulted in minimally increased risk
 * Conclusion: RS mildly elevates risk of IBC, but largely attributable to co-existent proliferative disease. Further interventions should be based on extent of atypical hyperplasia
 * Newcastle upon Tyne, 2005 (UK)(1988-2002) PMID 16024215 -- "All radial scars/complex sclerosing lesions seen on breast screening mammograms should be excised." (Fasih T, Eur J Surg Oncol. 2005 Dec;31(10):1125-8.)
 * Retrospective. 124 women from screening program, detected by mammogram, with histologically confirmed RS
 * Presence of RS: 66% pure radial scar, 18% ADH, 16% DCIS or invasive CA
 * Mammogram: If FNA, mammogram 5/9 malignancy; if localization Bx, mammogram 4/11 malignancy
 * Conclusion: All screen-detected stellate lesions should be excised due to association with pre-malignant and malignant disease


 * Melbourne, 2003 PMID 12518358 -- "Fourteen-gauge needle core biopsy of mammographically evident radial scars: is excision necessary?" (Cawson JN, Cancer. 2003 Jan 15;97(2):345-51.)
 * Prospective. 75 consecutive RS detected by mammogram from population-based screening. 55 patients stereotactic core Bx first, 8 patients US-guided core Bx first, followed by excision bx
 * Radial scar: overall 51/62 patients (82%). Sensitivity for stereotactic 85%, for US-guided 63%
 * Associated lesions: in 4 patients with DCIS on excision, stereotactic bx revealed ADH or DCIS (both of which require excision). No invasiave CA. ADH present in 57%, found on biopsy in 72%
 * Conclusion: Stereotactic core bx proven RS can be managed by mammography, provided there is no associated DCIS, ADH, or LCIS


 * John Wayne CI, 2002 PMID 12388495 -- "Percutaneous core needle biopsy of radial scars of the breast: when is excision necessary?" (Brenner RJ, AJR Am J Roentgenol. 2002 Nov;179(5):1179-84.)
 * Retrospective. 157 lesions treated with surgery (102) or followed by mammography (55)
 * CA risk: if ADH present, CA in 28%; if no atypia, CA in 4%.
 * Sensitivity: Missed in 9% of spring-loaded vs. 0% of vacuum-assisted (SS); missed in 8% if <12 samples vs. 0% if >=12 samples
 * Conclusion: RS diagnosis likely reliable if no ADH, bx includes >=12 specimens, and mammography agrees. If not, then need excisional bx


 * Nurses Health Study, 1999 PMID 9971867 -- "Radial scars in benign breast-biopsy specimens and the risk of breast cancer." (Jacobs TW, N Engl J Med 1999 Feb 11;340(6):430-6.)
 * Case-control. 1396 women from Nurses' Health Study, 255 women with BCA, 1141 controls. Median F/U 12 years
 * Radial scar: 99/1396 women (7.1%); mostly incidental finding (median 4.0 mm)
 * Cancer risk: Overall RR 1.8; if proliferative disease without atypia, RR 3.0 if RS vs. RR 1.5 if no RS; if proliferative disease with atypia, RR 5.8 if RS vs. RR 3.8 if no RS
 * Conclusion: RS is an independent histologic risk factor for BCA

Review

 * 2005 PMID 16034013 -- "Benign breast disorders." (Santen RJ, N Engl J Med. 2005 Jul 21;353(3):275-85.)