The Times, They are a Changin’: Breast Cancer Treatment in 2014

Someone recently said to me, “Change is inevitable, except from vending machines.” Nowhere is that claim more accurate than when it comes to breast cancer management. 

When I was in medical school, the approach of William Halsted (1852-1922) continued to reign supreme. To Halsted, breast cancer was an aggressive, local, regional disease. Therefore, curative treatment sought to eradicate all local expressions of the primary tumor. This could be accomplished with a mastectomy and radical axillary node dissection. However, the approach was disfiguring—and it did not cure the disease. 

I recently attended a Grand Rounds that reframed breast cancer for this generation and the future. Rather than Halsted’s local-regional characterization, breast cancer is now considered a systemic disease, with biological behaviors, consequent specific phenotypical expressions, and it needs to be treated with those realities in mind.^{1
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One example of the shifting focus from “local” to “systemic” thinking is the acceptance of lumpectomy as the definitive surgical treatment—so-called breast conserving therapy (BCT)—in contrast to a radical mastectomy.² 

What has happened to survival as a result? Patients undergoing BCT have a higher breast cancer-specific survival rate compared with individuals treated by mastectomy alone or with the addition of radiation.²

Another paradigm shift is the introduction of “personalized therapy.”³ Examining the breast tumor’s expression of 3 phenotypes—estrogen and progesterone receptors (ER and PR) and human epidermal growth factor 2 (HER2 or v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 [ERBB2])—has resulted in a accurate risk stratification after the diagnosis of breast cancer. 

Furthermore, the 3 phenotypes have changed approaches to prognostication: 

Best prognosis: ER+, PR+, and HER2– (Luminal A)

Second: ER+, PR+, and HER2+ (Luminal B)

Third: ER–, PR–, and HER2+

Worst:, ER–, PR–, and HER2– (all 3 expressions absent or the so-called “triple negative” disease)  

When the traditional “tumor, nodes, metastases” staging system is informed further by a triple negative phenotype, a more accurate prognosis is achieved. The phenotypic story does not end with prognosticating, HER2+ expression is now treated with phenotypically-targeted agents (eg, trastuzumab).  

Finally, let’s think back to Halsted. Since the prognosis for the triple negative phenotype is worse than other combinations, maybe that specific entity should still be treated by radical mastectomy. Research suggests that BCT is not associated with a worse prognosis in triple negative disease than a mastectomy.⁴

Despite Halsted’s contributions to surgery, his paradigm has been put to rest. Change in breast cancer treatment is a good thing. ■

Gregory W. Rutecki, MD, is a physician at the National Consult Service at the Cleveland Clinic. He is also a member of the editorial board of Consultant. Dr Rutecki reports that he has no relevant financial relationships to disclose.

Reference:

1. Abraham J. Breast cancer treatment present and future. Medical Division Grand Rounds. Cleveland Clinic. 2014 Mar 6.

2.Agarwal S, Pappas L, Neumayer L, et.al. Effect of breast conservation therapy vs. mastectomy on disease-specific survival for early-stage breast cancer. JAMA Surg. 2014;149(3):267-274.

3.Bagaria SP, Ray PS, Sim MS, et al. Personalizing breast cancer staging by the inclusion of ER, PR, and HER2. JAMA Surg. 2014;149(2):125-129.

4.Gangi A, Chung A, Mirocha J, et.al. Breast-conserving therapy for triple-negative breast cancer. JAMA Surg. 2014;
149(3):252-258.