Podcast: DCIS dilemma – Dr. Laura Esserman

Dr. Zsuzsanna Suba

Extended Comment
The low but consistent incidence rate of invasive breast cancer deriving from ductal in situ carcinoma (DCIS) justifies that the usual surgical and adjuvant therapy of high grade DCIS is not always capable of ensuring a tumor-free life, while low grade DCIS is perhaps superfluously over treated.
Appropriate estrogen receptor (ER)-signaling is the chief safeguard of genomic stability in strong interplay with DNA-controlling and repairing systems, such as BRCA-genes and their protein products [http://goo.gl/EsB1bK]. Detection of DCIS by mammographic screening may be regarded as an early marker of disturbed hormonal, metabolic and DNA-stabilizer equilibrium, since the female breast is exquisitely sensitive to the defects of estrogen signaling [http://goo.gl/xRh4wL]. The stronger the defect of cellular estrogen surveillance, the higher is the probability of DCIS development with high-risk characteristics.
Among young cases with active ovarian estrogen synthesis, the relatively higher risk of poorly differentiated DCIS may be attributed to the low incidence rate of more successfully suppressed ER-positive cancers rather than an excessive inclination to ER-negative tumors. Moreover, among dark-skinned American women, the higher risk of developing poorly differentiated DCIS and the higher breast cancer mortality rate as compared with white women are associated with estrogen deficiency and further hormonal defects. These endocrine disturbances may be explained by the incongruence between their excessive pigmentation and the poor light and sunshine exposure of North-America.
[http://dx.doi.org/10.2174/157489212801820048].
In women, during aging, progressive weakening of estrogen signaling and the associated gene stabilizer mechanisms are dangerous systemic processes [http://goo.gl/yiYszF], despite any usual, aggressive treatment of DCIS. In patients having increased risk of invasive breast cancer, natural estrogen substitution is the optimal risk-reducing therapy aiming the stabilization of gene regulatory processes and the apoptotic death of accidentally initiated tumor cells [http://dx.doi.org/10.2147/dddt.s89536]. By contrast, antiestrogen treatment against tumor recurrence may be risky, being effective only in such genetically proficient women who are capable of strong, counteractive upregulation of estrogen signaling. Tumor growth may be provoked by de novo or acquired antiestrogen resistance being associated with the missing capacity of patients for the extreme upregulation of estrogen signaling or with the exhaustion of defensive counteractions by excessive antiestrogen administration [http://dx.doi.org/10.2147/dddt.s89536].
In conclusion, in cases of DCIS which have been diagnosed, the most important preventive strategy against invasive breast cancer development is to combine lumpectomy with strict control and maintenance of estrogen signaling over a whole lifetime.
Zsuzsanna Suba