The Impact of Adding Radiation Treatment After Breast Conservation Surgery for Ductal Carcinoma In Situ of the Breast

Department of Radiation Oncology, Albert Einstein Medical Center, 5501 Old York Rd, Philadelphia, PA 19141, USA.
JNCI Monographs 10/2010; 2010(41):187-92. DOI: 10.1093/jncimonographs/lgq020
Source: PubMed


Ductal carcinoma in situ (DCIS; intraductal carcinoma) is most commonly detected as suspicious microcalcifications on routine
screening mammography in an asymptomatic woman. As most women with newly diagnosed DCIS are eligible for breast conservation
treatment, a major decision for most women is whether or not to add radiation treatment after surgical excision (lumpectomy).
In four prospective randomized clinical trials, the addition of radiation treatment after lumpectomy reduced the risk of local
recurrence by approximately 50%, both for overall local recurrence and for the subset of invasive local recurrence. Nonetheless,
efforts have continued to attempt to identify a subset of patients with favorable DCIS who are at sufficiently low risk of
local recurrence that omitting radiation treatment is reasonable. Prospective and retrospective studies have demonstrated
excellent long-term outcomes at 10 and 15 years after breast conservation treatment with radiation. Careful follow-up, including
yearly surveillance mammography, after initial breast conservation treatment with radiation is warranted for the early detection
of potentially salvageable local and local-regional recurrences.

Full-text preview

Available from:
  • Source
    • "Radiotherapy is one of the cornerstones in the treatment of patients with breast cancer [7,8]. Radiation greatly reduces the risk of recurrence in women with ductal carcinoma in situ[9,10] and in breast cancer patients who are lymph node positive [11-13]. The outcomes following chemotherapy vary depending on the subtype: for example, ER-PR-HER2- and ER-PR-HER2+ breast cancers respond better than luminal subtypes to anthracycline-based chemotherapies [14]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The discovery of molecular markers associated with various breast cancer subtypes has greatly improved the treatment and outcome of breast cancer patients. Unfortunately, breast cancer cells acquire resistance to various therapies. Mounting evidence suggests that resistance is rooted in the deregulation of the G1 phase regulatory machinery. To address whether deregulation of the G1 phase regulatory machinery contributes to radiotherapy resistance, the MCF10A immortalized human mammary epithelial cell line, ER-PR-Her2+ and ER-PR-Her2- breast cancer cell lines were irradiated. Colony formation assays measured radioresistance, while immunocytochemistry, Western blots, and flow cytometry measured the cell cycle, DNA replication, mitosis, apoptosis, and DNA breaks. Molecular markers common to all cell lines were overexpressed, including cyclin A1 and cyclin D1, which impinge on CDK2 and CDK4 activities, respectively. We addressed their potential role in radioresistance by generating cell lines stably expressing small hairpin RNAs (shRNA) against CDK2 and CDK4. None of the cell lines knocked down for CDK2 displayed radiosensitization. In contrast, all cell lines knocked down for CDK4 were significantly radiosensitized, and a CDK4/CDK6 inhibitor sensitized MDA-MB-468 to radiation induced apoptosis. Our data showed that silencing CDK4 significantly increases radiation induced cell apoptosis in cell lines without significantly altering cell cycle progression, or DNA repair after irradiation. Our results indicate lower levels of phospho-Bad at ser136 upon CDK4 silencing and ionizing radiation, which has been shown to signal apoptosis. Based on our data we conclude that knockdown of CDK4 activity sensitizes breast cancer cells to radiation by activating apoptosis pathways.
    Full-text · Article · Jul 2013 · Cell Division
  • Source
    • "With the advent of screening mammography, DCIS represents approximately 20% of all new cases of breast cancer diagnosed in the United States annually. Lumpectomy followed by radiation therapy (RT) is the most common treatment for DCIS, the efficacy of which is supported by randomized trials and meta-analysis demonstrating a reduction in the risk for local recurrence by approximately 50% [2,3]. Although the primary goal of therapy is to prevent invasive recurrence, 50% of all local recurrences after RT are invasive cancer [2]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Ductal carcinoma in situ (DCIS) is characterized by non-invasive cancerous cell growth within the breast ducts. Although radiotherapy is commonly used in the treatment of DCIS, the effect and molecular mechanism of ionizing radiation (IR) on DCIS are not well understood, and invasive recurrence following radiotherapy remains a significant clinical problem. This study investigated the effects of IR on a clinically relevant model of Akt-driven DCIS, and identified possible molecular mechanisms underlying invasive progression in surviving cells. We measured the level of phosphorylated-Akt (p-Akt) in a cohort of human DCIS specimens by immunohistochemistry (IHC) and correlated it with recurrence risk. To model human DCIS, we used Akt overexpressing human mammary epithelial cells (MCF10A-Akt), which, in 3-dimensional laminin-rich extracellular matrix (3D lrECM) and in vivo form organotypic DCIS-like lesions with lumena expanded by pleiomorphic cells contained within an intact basement membrane. In a population of cells that survived significant IR doses in 3D lrECM, a malignant phenotype emerged creating a model for invasive recurrence. P-Akt was up-regulated in clinical DCIS specimens, and was associated with recurrent disease. MCF10A-Akt cells that formed DCIS-like structures in 3D lrECM showed significant apoptosis after IR, preferentially in the luminal compartment. Strikingly, when cells that survived IR were repropagated in 3D lrECM, a malignant phenotype emerged, characterized by enhanced invasive activity, up-regulation of fibronectin, alpha5beta1-integrin, MMP-9 and loss of E-cadherin. In addition, IR induced nuclear translocation and binding of NF-kappaB to the beta1-integrin promoter region, associated with up-regulation of alpha5beta1-integrins. Inhibition of NF-kappaB or beta1-integrin signaling abrogated emergence of the invasive activity. P-Akt is up-regulated in some human DCIS lesions, and is possibly associated with recurrence. MCF10A-Akt cells form organotypic DCIS-like lesions in 3D lrECM and in vivo, and are a plausible model for some forms of human DCIS. A population of Akt-driven DCIS-like spheroids that survive IR progresses to an invasive phenotype in 3D lrECM mediated by beta1-integrin and NF-kappaB signaling.
    Full-text · Article · Jul 2013 · Breast cancer research: BCR
  • [Show abstract] [Hide abstract]
    ABSTRACT: Improved screening practices have lead to a dramatic increase in the diagnosis of ductal carcinoma in situ (DCIS) over the past 40 years. At present, it accounts for about 30% of newly diagnosed breast cancers.[1] Our current understanding of the natural history of DCIS indicates that it is an immediate, nonobligate precursor of invasive cancer. DCIS is confined to the breast parenchyma, but if it progresses to invasive breast cancer, the potential exists for the development of distant metastasis and subsequent death. The primary goal of treating DCIS is thus to prevent the development of invasive cancer. Treatment of DCIS is successful for most women; however, the disease can recur, and half of all local recurrences present as invasive breast cancer. At present, we still have a limited understanding of which cases of DCIS will ultimately progress to invasion and which cases will be resistant to therapy. Therefore, tailored management of DCIS is still a work in progress.
    No preview · Article · Aug 2011 · Oncology (Williston Park, N.Y.)
Show more