Outcome of patients with ductal carcinoma in situ untreated after diagnostic biopsy

Collins, Laura C.; Tamimi, Rulla M.; Baer, Heather J.; Connolly, James L.; Colditz, Graham A.; Schnitt, Stuart J.

doi:10.1002/cncr.20979

Cited by 260 publications

(180 citation statements)

References 24 publications

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“…Patients with DCIS (possibly the most prevalent precursor to invasive breast cancer [6][7][8][9][10][11]) currently undergo some combination of breast conserving surgery, radiation therapy, and hormonal therapy. Breast conserving surgery fails to remove the entire tumor 38-72% of the time, requiring up to three surgeries for adequate tumor excision [12][13][14].…”

Section: Introductionmentioning

confidence: 99%

A Novel, Patient-Specific Mathematical Pathology Approach for Assessment of Surgical Volume: Application to Ductal Carcinomain situof The Breast

Edgerton

Chuang

Macklin

et al. 2011

Analytical Cellular Pathology

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Abstract. We introduce a novel "mathematical pathology" approach, founded on a biophysical model, to identify robust patientspecific predictors of tumor growth useful in clinical practice to improve the accuracy of diagnosis/prognosis and intervention. In accordance with biological observations, our model simulates the diffusion-limited in-situ tumors with a relatively short phase of fast initial growth, followed by a prolonged slow-growth phase where tumor size is constrained primarily by the relative weight of cell mitosis and death. The former phase may only last for a few months, so that at the time of diagnosis, we may assume that most tumors will have entered the phase where their size is changing slowly. Based on this prediction, we hypothesize that the volume of breast with ducts affected by in-situ tumors at the time of diagnosis will be closely approximated by a modelderived mathematical function based on the ratio of tumor cell proliferation-to-apoptosis indices and on the extent of diffusion of cell nutrients (diffusion penetration length), which can be measured from immunohistochemical and morphometric analysis of patient histopathology specimens without the need for multiple-time measurements. We tested this idea in a retrospective study of 17 patients by staining breast tumor specimens containing ductal carcinoma in situ for mitosis with Ki-67 and for apoptosis with cleaved caspase-3 and counting cells positive for each marker. We also determined diffusion penetration by measuring the thickness of viable rims of tumor cells within ducts. Using the ensuing ratios, we applied the model to determine a predicted surgical volume or tumor size. We then corroborated our hypothesis by comparing the predicted size of each tumor based on our model with the actual size of the pathological specimen after tumor excision (R 2 = 0.74-0.88). In addition, for the 17 cases studied, both histological grade and mammography were not found to correlate with tumor size (R 2 = 0.08-0.47). We conclude that our mathematical pathology approach yields a high degree of accuracy in predicting the size of tumors based on the mitotic/apoptotic index and on diffusion penetration. By obtaining these ratios at the time of initial biopsy, pathologists can employ our model to predict the size of the tumor and thereby inform surgeons how much tissue to remove (surgical volume). We discuss how results from the model have implications concerning the current debate on recommendations for screening mammography, while the model itself may contribute to better planning of breast conservation surgery.

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Section: Introductionmentioning

confidence: 99%

A Novel, Patient-Specific Mathematical Pathology Approach for Assessment of Surgical Volume: Application to Ductal Carcinomain situof The Breast

Edgerton

Chuang

Macklin

et al. 2011

Analytical Cellular Pathology

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“…However, recurrence with metastasis occurs in a significant fraction of women with stage I cancers; if such tumors could be prospectively identified, it would be possible to preemptively adopt a more aggressive therapy. Conversely, even though the standard treatment is curative for DCIS, more than half of these lesions are indolent and would never become life-threatening if left untreated (7)(8)(9), indicating that there is systematic overtreatment of a significant fraction of patients with DCIS. Collectively, these considerations underscore the importance of defining the genetic drivers of DCIS progression.…”

mentioning

confidence: 99%

SMARCE1 is required for the invasive progression of in situ cancers

Sokol

Feng

Jin

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Advances in mammography have sparked an exponential increase in the detection of early-stage breast lesions, most commonly ductal carcinoma in situ (DCIS). More than 50% of DCIS lesions are benign and will remain indolent, never progressing to invasive cancers. However, the factors that promote DCIS invasion remain poorly understood. Here, we show that SMARCE1 is required for the invasive progression of DCIS and other early-stage tumors. We show that SMARCE1 drives invasion by regulating the expression of secreted proteases that degrade basement membrane, an ECM barrier surrounding all epithelial tissues. In functional studies, SMARCE1 promotes invasion of in situ cancers growing within primary human mammary tissues and is also required for metastasis in vivo. Mechanistically, SMARCE1 drives invasion by forming a SWI/SNF-independent complex with the transcription factor ILF3. In patients diagnosed with early-stage cancers, SMARCE1 expression is a strong predictor of eventual relapse and metastasis. Collectively, these findings establish SMARCE1 as a key driver of invasive progression in early-stage tumors.T he past two decades have brought an exponential increase in the diagnosis of early-stage breast lesions, most commonly ductal carcinoma in situ (DCIS). DCIS remains encapsulated within the ductal-lobular architecture of mammary epithelium; in contrast, invasive breast cancers have escaped this architecture by breaking through the basement membrane, a layer of ECM rich in collagen (IV) and laminins that separates epithelial tissues from the adjacent stromal microenvironment ( Fig. S1A) (1). This distinction has a critical impact on patient prognosis: whereas women with DCIS show no reduction in survival 5 y after diagnosis, those with invasive cancers have a 15-74% reduction in 5-y survival rates depending on the extent of tumor invasion at diagnosis (2). Given these observations, there is significant interest in finding genes that promote the invasive progression of early-stage tumors (3). Previous studies have sought molecular alterations present in invasive tumors but not DCIS, leading to the identification of hundreds of genomic and gene-expression alterations specifically associated with invasive cancers (4-6). However, it is unclear if genes that are amplified or up-regulated in invasive cancers also functionally drive DCIS invasion. In large part, the difficulty in addressing this question can be traced to a paucity of experimental systems that model cancer invasion within a microenvironment that faithfully replicates human breast tissue.The treatment of early-stage cancers remains an unresolved issue. Women with early-stage breast cancers-which include DCIS and stage I tumors that have not entered the lymph nodesare typically treated by lumpectomy followed by localized radiation. However, recurrence with metastasis occurs in a significant fraction of women with stage I cancers; if such tumors could be prospectively identified, it would be possible to preemptively adopt a more aggressive therapy. Conver...

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“…The condition is more common in women, representing 20% of breast cancer cases, with fewer high-grade intraductal papillary cases than are seen in men 10 . Of all male and female patients with dcis, 30%-50% eventually develop invasive cancer in the subsequent 10-20 years, and so the actual prevalence in the general population may be higher 11 . The causes of dcis in men are unknown, because men lack the terminal duct lobular unit (tdlu) in which dcis frequently originates in women 9 .…”

Section: Discussionmentioning

confidence: 99%

Ductal Carcinoma In Situ in a 25-Year-Old Man Presenting with Apparent Unilateral Gynecomastia

Coroneos

Hamm

2010

Current Oncology

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Ductal carcinoma in situ (dcis) in a young man is rarely reported. Our patient, a 25-year-old man, presented with apparent symptomatic unilateral gynecomastia. He has a strong history of cancer on both the maternal and paternal sides of his family, including breast and lung (maternal) and melanoma, colon, and pancreatic (paternal). His mother tested negative for BRCA1 and BRCA2. There is no information on paternal genetic testing.The patient was treated with left subcutaneous mastectomy. Upon histologic review of the sample, concurrent gynecomastia and dcis were discovered. To date, only 4 cases of gynecomastia and dcis have been described in younger male patients. Because only 30%-50% of patients with dcis eventually develop invasive cancer in the subsequent 10-20 years, dcis prevalence in the general population may be higher than predicted. This case underscores the importance of family history in any patient presenting with a breast mass. Patients must be made aware of the risk, however small it may be, and physicians must remain cautious of cancer in young men with gynecomastia. KEY WORDSGynecomastia, ductal carcinoma in situ, male breast cancer

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Outcome of patients with ductal carcinoma in situ untreated after diagnostic biopsy

Cited by 260 publications

References 24 publications

A Novel, Patient-Specific Mathematical Pathology Approach for Assessment of Surgical Volume: Application to Ductal Carcinomain situof The Breast

A Novel, Patient-Specific Mathematical Pathology Approach for Assessment of Surgical Volume: Application to Ductal Carcinomain situof The Breast

SMARCE1 is required for the invasive progression of in situ cancers

Ductal Carcinoma In Situ in a 25-Year-Old Man Presenting with Apparent Unilateral Gynecomastia

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