Ductal Carcinoma Insitu

• Ductal carcinoma in situ (DCIS):
  • Is a malignant intra-ductal proliferation of epithelial cells within the tubular-lobular system of the breast:
    • With no microscopic evidence of permeation across the basement membrane
• There appears to be a progression between:
  • Flat epithelial atypia, atypical ductal hyperplasia (ADH), and DCIS:
    • In which DCIS is final step prior to the development of invasive disease
• The clinical risk factors and molecular aberrations related with malignant transformation:
  • Are almost indistinguishable between DCIS and invasive cancer
• The concurrence of DCIS and invasive carcinoma within one lesion suggests that:
  • DCIS is a precursor lesion to invasive carcinoma
• Evidence of the ability of DCIS to progress is that:
  • 50% of all recurrences after breast-conserving surgery (BCS) for DCIS, with or without adjuvant treatment, are invasive
• Data is sparse on the natural history of DCIS:
  • But some series have reported the outcomes for women many years after undergoing a surgical biopsy that was interpreted as benign that contained an unrecognized area of DCIS:
    • These data identified that approximately 20% to 53% of these women developed:
      • Ipsilateral invasive carcinoma
  • Sanders et al. reported on 28 women with unrecognized low-grade DCIS in the surgical biopsy specimen:
    • Of which 11 developed invasive carcinoma:
      • All of these cancers developed in the same breast and quadrant as the biopsy containing the DCIS
  • The vast majority of these invasive cancers developed within 10 years, but three were diagnosed after 20 years
  • Collins et al, in the Nurses’ Health Study, singled out 13 women who were found to have DCIS on reexamination of the surgical biopsies that were previously diagnosed as benign:
    • Ten of these women subsequently developed breast cancer
      • All were ipsilateral
      • Four were DCIS and six were invasive
      • The interval between the biopsy and the progression to invasive cancer was on average nine years
• Approximately one in eight women (12%) in the United States (US) will be diagnosed with breast cancer in her lifetime:
  • 20% to 25% of these newly diagnosed cases will be DCIS (Siegel 2015, CA Cancer J Clin)
• In 2020, an estimated 51, 400 cases of DCIS will be diagnosed in US
• Universal screening mammography:
  • Has resulted in a 10-fold increase in the incidence of DCIS since the mid-1980s:
    • But since 2003:
      • The incidence of DCIS has decreased in women age 50 years and older:
        • Conceivably secondary to decline in the use of hormone replacement therapy
      • While the incidence in women younger than 50 continues to increase:
        • Altekruse SF, Kosary CL, Krapcho M, et al.: SEER Cancer Statistics Review, 1975-2007. Bethesda, Md: National Cancer Institute, 2010. Also available online. Last accessed April 3, 2020
  • Roughly one in every 1,300 mammograms performed in US:
    • Will lead to a diagnosis of DCIS:
      • Representing 17% to 34% of all mammographically detected breast cancers
  • Before the institution of widespread screening mammography in the mid-1980s:
    • Most of the cases of DCIS were not identified until a palpable tumor developed:
      • But today:
        • 80% to 85% of DCIS cases are screen detected
• The incidence of DCIS in necropsy studies is higher than in the general population:
  • Proposing that not all DCIS lesions become clinically significant:
    • Supporting concerns that most of the increase in DCIS incidence is due to the detection of non-aggressive subtypes:
      • That are unlikely to progress to invasive cancer
• Most women with DCIS are diagnosed at a median age:
  • That ranges from 47 to 63 years:
    • Similar to that reported for patients with invasive carcinoma
  • However, the age of peak incidence for DCIS (96.7 per 100,000 women):
    • Occurs between the ages of 65 and 69 years:
      • Which is younger than that for invasive breast cancer:
        • For which peak incidence (453.1 per 100,000 women):
          • Occurs between the ages of 75 and 79 years
• The incidence of first-degree relatives having breast cancer (i.e., 10% to 35%) as well as deleterious mutations in the breast cancer associated (BRCA) genes:
  • Are similar for patients with DCIS as for women with invasive breast cancer
• Other risk factors for DCIS include:
  • Older age
  • Proliferative breast disease
  • Increased breast density
  • Nulliparity
  • Older age at first live birth
  • History of breast biopsy
  • Early menarche
  • Late menopause
  • Long-term use of postmenopausal hormone replacement therapy
  • Elevated body mass index in postmenopausal women
    • Are the same as those for invasive breast cancer, but in many cases:
      • The relationship between a given characteristic and invasive cancer is stronger than the relationship between that characteristic and DCIS

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