Selecting Individualized Treatment for Patients With Ductal Carcinoma in Situ of the Breast: The Search Continues

Abstract

The management of ductal carcinoma in situ (DCIS; intraductal carcinoma) of the breast is controversial. Consider a hyphothetical patient with a typical clinical presentation. An asymptomatic, healthy 60-year-old woman is found on routine screening mammography to have a small area of suspicious microcalcifications. Core biopsy and subsequent surgical excision demonstrate grade 2 DCIS, 1.0 cm in size, with negative margins of resection. Should the patient be treated with radiation, tamoxifen, both, or neither? The best management for such a patient has been debated for decades. DCIS of the breast is most commonly detected in the asymptomatic woman as a small area of abnormal calcifications on routine screening mammography. In this setting, most women have a limited extent of disease, are eligible for breast conservation treatment, and fortunately do not require a mastectomy. DCIS can be a precursor for development of a subsequent invasive breast carcinoma in some patients. The goal of adding radiation treatment after surgical excision (lumpectomy) is to reduce the risk of local recurrence in the breast (also known as an ipsilateral breast event or ipsilateral breast tumor recurrence). Local treatment options for DCIS include lumpectomy plus radiation treatment, lumpectomy alone without radiation treatment, or mastectomy. Tamoxifen can also be considered as a systemic treatment option. Because most patients with DCIS are eligible for breast conservation treatment, a key management decision often is whether to add radiation treatmentand/or tamoxifenafter lumpectomy.Thisdecisionrequires the physiciantoestimatetheriskof localrecurrence, invasivelocalrecurrence, and all breast cancer events (defined as combined ipsilateral plus contralateral breast events) if the patient were to be treated with lumpectomy alone or without radiation treatment or tamoxifen. Although some patients with DCIS will develop a subsequent invasive breast malignancy over time, most patients will not. Current clinical and pathologic parameters are imperfect in predicting which patients will develop an invasive breast malignancy. Thus, many patients and physicians will elect to add radiation treatment and tamoxifen after lumpectomy with the goal of reducing and minimizing the risk of developing a subsequent local recurrence or invasive local recurrence. The dilemma of managing DCIS is further compounded by the knowledge that initial treatment with an ipsilateral mastectomy is associated with minimal or no risk of local recurrence but is a severe price to pay as a preventive measure for the asymptomatic patient without a known invasive breast malignancy at presentation. Most patients with DCIS elect breast conservation treatment in contemporary practice. However, many patients also elect adjuvant treatment with radiation and tamoxifen to reduce risk, especially the risk of a subsequent invasive breast malignancy, while recognizing that such an approach overtreats most patients. Giventheuncertainties inselectingtreatmentforDCIS,patientsand physicians would greatly benefit from a tool that could improve clinical decision making. In a previous issue of Journal of Clinical Oncology, Rudloffetal oftheMemorialSloan-KetteringCancerCenter(MSKCC;New York, NY) reported an internally validated nomogram to predict the risk of local recurrence for patients with DCIS of the breast. The 10 clinical and pathologic variables included in the nomogram were: patient age at diagnosis, family history, initial presentation, radiation treatment, adjuvant endocrine therapy, nuclear grade, necrosis, margins of resection, number of surgical excisions, and year of surgery. Using these variables, the 5and 10-year probabilities of local recurrence for individual patients can be estimated. A validated MSKCC nomogram would aid clinical decision making by providing a baseline risk of local recurrence with neither radiation nor adjuvant endocrine treatment for the specific individual patient and by its ability to predict the potential gain of adding adjuvant treatments after lumpectomy. Such an approach would facilitate an individualized and tailored treatment discussion for the patient with DCIS, albeit based on conventional clinical and pathologic parameters. Because radiation reduces ipsilateral local recurrence (invasive carcinoma or DCIS) by approximately 50%, and because tamoxifen reduces all breast cancer events (combined ipsilateral plus contralateral) by approximately 30%, one can estimate the potential absolute gains of adding radiation treatment and tamoxifen. Risk-benefit ratios can then be evaluated for adding radiation treatment, tamoxifen, or both, given their known potential adverse effects. To return to the hyphothetical patient with DCIS, the MSKCC nomogram could be used to predict the 5and 10-year risks of local recurrence and invasive local recurrence for this specific clinical presentation (Table 1). For this hyphothetical patient, adding radiation treatment plus tamoxifen after surgical excision would reduce the predicted the 10-year risk of local recurrence by 11% (from 13% to 2%) and invasive local recurrence by 5.5% (from 6.5% to 1%), which many patients and physicians would consider sufficiently large to warrant treatment. Thus, the MSKCC nomogram potentially gives the individual patient and her physician meaningful information to base a discussion of individualized local recurrence risks and potential gains for adding adjuvant treatment after surgical excision. In the article that accompanies this editorial, Yi et al now report their attempt to validate the previously published MSKCC nomogram for predicting local recurrence. The authors studied 794 patients with DCIS from the MD Anderson Cancer Center treated with surgical excision between 1990 and 2007. The study population largely consisted of patients with favorable DCIS lesions. The majority of the DCIS lesions initially presented with Editorials