Radiation Oncology/Breast/Benign

Relative Risk of Developing BCA (PMID 16034013)

Risk	Proliferation	Histology	Specific Findings
No increase	Nonproliferative/ minimal (67%)	Fibrocystic changes	Cysts & ductal ectasia, mild hyperplasia, nonsclerosis adenosis, periductal fibrosis, simple fibroadenoma
		Benign tumors	Hamartoma, lipoma, phyllodes tumor (some have malignant features), solitary papilloma, neurofibroma, giant adenoma, adenomyoepithelioma
		Traumatic lesions	Hematoma, fat necrosis, foreign body penetration
		Infections	Granuloma, mastitis
		Sarcoidosis
		Metaplasia	Squamous, apocrine
		Diabetic mastopathy
Small increase (RR 1.5-2.0)	Proliferative, no atypia (30%)	Usual ductal hyperplasia, complex fibroadenoma, papilloma/papillomatosis, radial scar, blunt duct adenosis
Moderate increase (RR >2.0)	Proliferative, with atypia (4%)	Atypical ductal hyperplasia, atypical lobular hyperplasia

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.)