Ten Years after Human Genome Sequencing: Is Personalized Breast Screening and Prevention Reality?

Abstract

To the Editor, In the May issue of the World Journal of Surgery, Bennett and colleagues reported the results of multimodality breast screening for women at high risk of developing breast cancer. Are we able—nearly a decade since the completion of the draft sequence of the human genome—to translate the major advances in biotechnology, DNA sequence, and basic sciences to stratify women in the general population according to their breast-cancer risk for personalized screening and individualized primary prevention? In 1999, Bennett et al. [1], recognizing the need for personalized screening, established a Familial Breast Cancer Screening Clinic (FBCSC) program for women with breast cancer family history and increased risk of breast cancer. Since its inception, a total of 2,440 women have participated in the FBCSC clinical breast examination, breast ultrasound, and mammography. The authors conclude that multimodality screening for these women was effective and appropriate. During the past decade, rapid advances have been made in screening and primary prevention of women at risk of hereditary breast ovarian cancer (HBOC) syndrome. Genetic testing for identifying carriers of mutations in BRCA1 and BRCA2 (BRCA1/2) genes has been available, and breast magnetic resonance imaging has been recommended by recent guidelines for women at increased risk of breast cancer. However, several questions grow the uncertainty. Do women with positive BRCA1/2 testing benefit more from prophylactic bilateral mastectomy, bilateral salpingo-oophorectomy, or intensified surveillance? What is the optimal screening for women with family history but BRCA1/2-negative testing? Given that these heritable BRCA mutations with large effect on breast-cancer risk are very rare in the general population, what is the management of the vast majority of women in the general population without family history? The landmark achievement of the completion of the draft sequence of the human genome a decade ago raised excitement that would lead to a new era of molecular medicine and new ways to prevent, diagnose, treat, and cure complex diseases as cancer. However, despite research and technology rapid advances in the past decade, has human health truly benefited from the sequencing of the human genome? The leaders of the public and private efforts for the completion of human genome sequencing, Francis Collins and Craig Venter, both say ‘‘not much’’ [2, 3]. Indeed, a large-scale study based on newly discovered genetic variants provided negative results. In this study published in the New England Journal of Medicine, the addition of ten SNPs in standard breast cancer risk factors was not associated with a significant increase in the prediction risk of women who participated in this study [4]. In a recent editorial in the journal Nature for the first postgenomic decade era, it is emphasized that the astounding technological and intellectual advances should include equally astounding applications to human health in the next decade [5]. But because of the high complexity and heterogeneity of breast cancer, it is unknown whether primary prevention of women in the general population and cure of patients with breast cancer can be achieved within the next C. Katsios Department of Surgery, University of Ioannina, School of Medicine, Ioannina 451 10, Greece e-mail: chkatsios@gmail.com