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Current Opinion in Obstetrics & Gynecology:
doi: 10.1097/GCO.0b013e32835c5e36
BREAST CANCER: Edited by Gottfried E. Konecny

Impact of molecular breast cancer portraits on new treatment strategies for gynecologic malignancies

Konecny, Gottfried E.

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David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA

Correspondence to Gottfried E. Konecny, MD, David Geffen School of Medicine, University of California Los Angeles, 2825 Santa Monica Blvd., Suite 200, Santa Monica, CA 90404–2429, USA. Tel: +1 310 586 2652; fax: +1 310 586 0841; e-mail: gkonecny@mednet.ucla.edu

In most regions of the world treatment of breast cancer is primarily the responsibility of surgical oncologists and medical oncologists. As such, the question arises why would gynecologists or gynecologic oncologists, whose primary focus of interest is to treat gynecologic malignancies such as ovarian, endometrial or cervical cancer, be interested in learning about new developments for the treatment of breast cancer. The five reviews on breast cancer included in this issue of Current Opinion in Obstetrics and Gynecology will give us an answer to this question. It can be assumed without doubt that understanding successful breast cancer treatment approaches and applying these same strategies to gynecologic malignancies could transform the dismal prospects patients face when diagnosed with ovarian cancer or advanced endometrial and cervical cancer. The need to learn from breast cancer is further underscored by the fact that the mortality rates for ovarian cancer are essentially unchanged over the past 30 years [1–3]. Similarly, the mortality rates for endometrial cancer are unchanged over the past decades [4], and in fact have risen by almost a fifth over the past 10 years in some developed countries [5]. In stark contrast, in most developed nations breast cancer mortality has been dropping over the past decade and researchers say this is not solely due to improved breast cancer screening but due to better treatments that have become available over the past decade [6].

The successes that have been achieved in the treatment of breast cancer are in part due to the fundamental appreciation that breast cancer does not represent a single pathologic entity. Depending on the genes/pathways responsible for driving a specific subtype, the therapeutic approaches should be and are significantly different. Examples for breast cancer include the original appreciation that some breast cancers are driven by steroid hormones and their cognate receptors, whereas others are not, leading to use of tamoxifen only in tumors driven by hormone receptors. This was the first example of a useful molecularly targeted therapy linked to an effective biomarker. Others like trastuzumab or lapatinib then followed; each targeting a specific subgroup and/or molecular alteration within a disease histology and each making a significant positive impact on that subgroup specifically.

Using five high-information content platforms on breast cancer tumors from 463 patients (Agilent mRNA expression arrays, Illumina DNA methylation arrays, Affymetrix single nucleotide arrays, miRNA and whole-exome sequencing), the Cancer Genome Atlas (TCGA) Network has recently confirmed that there are four primary subtypes of breast cancer, each with its own biology and prognostic relevance: HER2-enriched, luminal A, luminal B and basal-like. A fifth type, called normal-like, was observed, but because of small numbers it was not rigorously studied [7].

Each of the subsequent reviews included in this issue of Current Opinion in Obstetrics and Gynecology will demonstrate how preclinical and clinical breast cancer research is leading the way to move us away from the ‘one-size-fits-all’ approach that has delayed the development of novel targeted cancer therapies for so long and is moving us toward newer tailored treatments for individual patients. Shastry et al.[8] provide an update on recent studies in basal-like and triple negative breast cancer and demonstrate that basal-like breast cancers share many genetic features with high-grade serous ovarian cancer and that both might be susceptible to agents that inhibit angiogenesis, as well as to compounds that target DNA repair. Howell [9] reviews several key trials that help define the optimal sequence of endocrine agents and approaches to overcome endocrine resistance in luminal A and luminal B breast cancer, findings that may in fact have great importance for the treatment of endometrial cancer. Konecny [10] reviews recent findings on mechanisms of intrinsic and acquired resistance to single-agent regimens inhibiting HER2, and highlights how the treatment paradigm for HER2-positive breast cancer is shifting toward a dual anti-HER2 therapeutic approach. Given the high prevalence of intrinsic and acquired resistance to single-agent targeted regimens, these findings might have important implications for how we design future studies in gynecologic malignancies. The review of von Minckwitz et al.[11] highlights recent neoadjuvant clinical trials in breast cancer and shows the utility of neoadjuvant treatment approaches to expedite drug development for specific breast cancer subtypes by allowing the immediate assessment of in-vivo response to systemic treatment using the pathological complete response rate as a surrogate marker for long-term clinical outcome. Neoadjuvant treatment approaches for ovarian cancer may similarly allow us to speed up drug development and reduce morbidity in this disease. Finally, Karam [12] comprehensively reviews the latest developments in breast cancer surgery which are aimed at reducing morbidity and improving cosmetic results of breast cancer surgery. His review includes updates on the reliability and safety of sentinel lymph node mapping in breast cancer which could prove to become a new minimally invasive surgical approach for endometrial cancer [12].

The traditional ‘one-size-fits-all’ treatment paradigms that have delayed progress in gynecologic oncology have ignored the fundamental concept that gynecologic malignancies, just like breast cancer, are heterogeneous diseases in terms of underlying genomic origins and molecular evolution. As such, it is likely that a better understanding of their molecular heterogeneity will have a dramatic impact on ovarian and endometrial cancer treatment similar to what is described in this issue of Current Opinion in Obstetrics and Gynecology for the treatment of breast cancer.

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Acknowledgements

None.

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Conflicts of interest

G.E.K. has received honoraria from Genentech, Sanofi-Aventis, Novartis and Amgen.

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REFERENCES

1. Barnholtz-Sloan JS, Schwartz AG, Qureshi F, et al. Ovarian cancer: changes in patterns at diagnosis and relative survival over the last three decades. Am J Obstet Gynecol 2003; 189:1120–1127.

2. http://http://www.cancer.org/Cancer/OvarianCancer/DetailedGuide/ovarian-cancer-key-statistics. Accessed November 2012.

3. http://seer.cancer.gov/csr/1975_2008/results_merged/topic_prevcounts.pdf. Accessed November 2012.

4. http://seer.cancer.gov/faststats. Accessed November 2012.

5. Office for National Statistics Mortality Statistics: deaths registered in 2010, England and Wales 2010, National Statistics: London.

6. Autier P, Boniol M, Gavin A, et al. Breast cancer mortality in neighbouring European countries with different levels of screening but similar access to treatment: trend analysis of WHO mortality database. Br Med J 2011; 343:d4411.

7. Cancer Genome Atlas Network. Comprehensive molecular portraits of human breast tumours. Nature 2012; 490:61–70.

8. Shastry M, Yardley DA. Updates in the treatment of basal/triple-negative breast cancer. Curr Opin Obstet Gynecol 2013; 25:40–48.

9. Howell SJ. Advances in the treatment of luminal breast cancer. Curr Opin Obstet Gynecol 2013; 25:49–54.

10. Konecny GE. Emerging strategies for the dual inhibition of HER2-positive breast cancer. Curr Opin Obstet Gynecol 2013; 25:55–65.

11. von Minckwitz G, Untch M, Loibl S. Update on neoadjuvant/preoperative therapy of breast cancer: experiences from the German Breast Group. Curr Opin Obstet Gynecol 2013; 25:66–73.

12. Karam A. Update on breast cancer surgery approaches. Curr Opin Obstet Gynecol 2013; 25:74–80.

© 2013 Lippincott Williams & Wilkins, Inc.

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