SABCS 2011 Report – Clarifying the risk of breast cancer in women with atypical breast lesions

by Dr Sunil Upadhyay – We know that atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), lobular carcinoma in-situ (LCIS) and borderline DCIS/severe ADH are breast lesions which can a high risk of developing into invasive breast cancer. However, the magnitude of risk and the efficacy of chemo-preventive measures remain unpredictable, when used in the clinical setting.

Investigators looked at the pathology data available from 1987-2010 at Massachusetts General, Brigham and Women’s and Newton Wellesley Hospitals in the USA to quantify the risk of progression to invasive tumour along with the effect of chemo-prevention from 1999 onward. They developed a trumping order to a single diagnosis to each patient feeling that border line DCIS was more likely to develop into invasive cancer compared to LCIS followed by ALD then ADH in that order. Whether or not chemo-prevention had been given was also assessed. The duration of chemo-prevention or agents used was not analysed. There were 76,333 breast pathology reports in 42,950 individuals of which 2942 women had atypical breast lesions.

The mean age was 53 years (19-93) with a mean follow-up of 66 months. ADH was the most common diagnosis (41%), ALH 28%, LCS 19% and borderline DCIS 12%. To understand the natural history of these lesions, they looked at the tissue from patients who have never received any chemo-prevention during their lifetime.

Invasive vs DCIS (no chemo-prevention)

No of cancers	Invasive cancer %	Non-invasive cancer %
ADH (n=57)	47.4	52.6
Borderline (n=21)	57.1	42.9
ALH (n=61)	68.9	31.1
LCIS (n=45)	71.1	28.9

• Invasive vs non-invasive cancer
• ADH and borderline: no significant difference
• ALH and LCS p< 0.001

There were 2460 patients who had received chemo-prevention from 1999 and beyond. 466 (18.9%) were treated with tamoxifen, raloxifene and/or exemestane to various lengths of time. 1472 (59.8%) patients were not treated and for 522 (21.2%) patients the data was unavailable. The results showed a very clear effect of chemo-prevention. At 5 years the risk dropped by 50% from 8.3 to 4.1% and at 10 year by about 66% from 21.3% to 7.5% (p=0.05). This drop was noted for all subtypes of these atypical lesions.

The investigators concluded that ADH, ALH, LCIS and borderline DCIS increase a woman’s risk of breast cancer and by a similar amount. Chemo-prevention for all atypical types of lesions significantly reduces breast cancer risk at 5 as well as 10 years. The increased use of chemo-prevention for patients with atypia will significantly decrease cancer risk. The investigators plan to use these data to create a better model of breast cancer risk prediction based on atypia type and use of chemo-prevention.

In this observation, only about 20% of patients took these medications. Therefore, there is plenty of room for improvement to reduce the risk of breast cancer. Unfortunately, the optimum duration of chemo-prevention therapy, best age to initiate and the most effective agent remains unknown. Development of a better model remains highly desirable. (Abstract S 4-4)