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Breast cancer in situ
Other names	Intraductal carcinoma
Ducts of themammary gland, the location of ductal carcinoma
Specialty	Oncology

Ductal carcinomain situ (DCIS), also known asintraductal carcinoma, is a pre-cancerous or non-invasive cancerous lesion of thebreast.^[1][2] DCIS is classified asStage 0.^[3] It rarely produces symptoms or a breast lump that can be felt, typically being detected throughscreening mammography.^[4][5] It has been diagnosed in a significant percentage of men (seemale breast cancer).^[6]

In DCIS, abnormal cells are found in the lining of one or moremilk ducts in the breast.In situ means "in place" and refers to the fact that the abnormal cells have not moved out of the mammary duct and into any of the surrounding tissues in the breast ("pre-cancerous" indicates that it has not yet become aninvasive cancer). In some cases, DCIS may become invasive and spread to other tissues, but there is no way of determining which lesions will remain stable without treatment, and which will go on to become invasive.^[7] DCIS encompasses a wide spectrum of diseases ranging from low-grade lesions that are not life-threatening to high-grade (i.e., potentially highly aggressive) lesions.

DCIS has been classified according to the architectural pattern of the cells (solid, cribriform, papillary, and micropapillary),tumor grade (high, intermediate, and low grade), or the presence or absence ofcomedo histology;^[8] or, in the case of theapocrine cell-based in situ carcinoma,apocrine ductal carcinomain situ, it may be classified according to the cell type forming the lesion.^[9] DCIS can be detected onmammograms by examining tiny specks of calcium known asmicrocalcifications. Since suspicious groups of microcalcifications can appear even in the absence of DCIS, abiopsy may be necessary for diagnosis.

About 20–30% of those who do not receive treatment developbreast cancer.^[10][11] DCIS is the most common type of pre-cancer in women. There is some disagreement on its status as cancer; some bodies include DCIS when calculating breast cancer statistics, while others do not.^[12][13]

Ductal carcinomain situ (DCIS) literally means groups of "cancerous"epithelial cells which remain in their normal location (in situ) within theducts and lobules of the mammary gland.^[14] Clinically, DCIS is considered to be apremalignant (i.e. potentiallymalignant) condition,^[15] because the biologically abnormal cells have not yet crossed thebasement membrane to invade the surrounding tissue.^[14][16] When multiple lesions (known as "foci" of DCIS) are present in differentquadrants of the breast, this is referred to as "multicentric" disease.^[8]

Forstatistical purposes, DCIS is sometimes counted as a "cancer", but this is not always the case.^[13][17] When classified as a cancer, it is referred to as a "non-invasive" or "pre-invasive" form.^[14][18] It is described by theNational Cancer Institute as a "noninvasive condition".^[13]

Most of the women who develop DCIS do not experience any symptoms. The majority of cases (80-85%) are detected through screening mammography. The first signs and symptoms may appear if the cancer advances. Because of the lack of early symptoms, DCIS is most often detected atscreening mammography.

In a few cases, DCIS may cause:

• A lump or thickening in or near the breast or under thearm
• A change in the size or shape of the breast
• Nipple discharge or nipple tenderness; the nipple may also be inverted, or pulled back into the breast
• Ridges or pitting of the breast; theskin may look like the skin of anorange
• A change in the way the skin of the breast,areola, or nipple looks or feels^[19] such as warmth,swelling, redness or scaliness.^[20]

The specific causes of DCIS are still unknown. The risk factors for developing this condition are similar to those for invasive breast cancer.^[21]

Some women are however more prone than others to developing DCIS. Women considered at higher risks are those who have afamily history of breast cancer, those who have had theirperiods at an early age or who have had a latemenopause. Also, women who have never hadchildren or had them late in life are also more likely to get this condition.

Long-term use of estrogen-progestin hormone replacement therapy (HRT) for more than five years after menopause, genetic mutations (BRCA1 or BRCA2 genes), atypicalhyperplasia, as well asradiation exposure or exposure to certainchemicals may also contribute in the development of the condition.^[22] Nonetheless, the risk of developing noninvasive cancer increases with age and it is higher in women older than 45 years.

80% of cases in the United States are detected by mammography screening.^[23] More definitive diagnosis is made bybreast biopsy forhistopathology.

• 
  Mammogram microcalcifications in ductal carcinomain situ
• 
  Histopathology of dystrophicmicrocalcifications in DCIS, H&E stain.
• 
  Histopathologic architectural patterns of DCIS.^[24]
• 
  Histopathology of high-grade DCIS. H&E stain.
  RBC =red blood cell.^[25]
• 
  DCIS withmicroinvasion, defined as focus of invasive cancer measuring up to 1.0 mm in size.^[26]
• 
  Immunohistochemistry for calponin in ductal carcinomain situ, highlighting myoepithelial cells around all tumor cells, thereby ruling outinvasive ductal carcinoma.
• 
  Ductal carcinomain situ with comedo necrosis spanning 30% of its diameter, which is generally regarded as the minimal size to classify it as comedo.^[27]

There are different opinions on the best treatment of DCIS.^[28] Surgical removal, with or withoutadditionalradiation therapy ortamoxifen, is the recommended treatment for DCIS by theNational Cancer Institute.^[29] Surgery may be either a breast-conservinglumpectomy or amastectomy (complete or partial removal of the affected breast).^[30] If a lumpectomy is used it is often combined with radiation therapy.^[13] Tamoxifen may be used ashormonal therapy if the cells showestrogen receptor positivity.^[13] Research shows that survival is the same with lumpectomy as it is with mastectomy, whether or not a woman has radiation after lumpectomy.^[31]Chemotherapy is not needed for DCIS since the disease is noninvasive.^[32]

While surgery reduces the risk of subsequent cancer, many people never develop cancer even without treatment and the associated side effects.^[30] There is no evidence comparing surgery withwatchful waiting and some feel watchful waiting may be a reasonable option in certain cases.^[30]

Use ofradiation therapy after lumpectomy provides equivalentsurvival rates to mastectomy, although there is a slightly higher risk of recurrent disease in the same breast in the form of further DCIS or invasive breast cancer.Systematic reviews (including aCochrane review) indicate that the addition of radiation therapy to lumpectomy reduces recurrence of DCIS or later onset of invasive breast cancer in comparison with breast-conserving surgery alone, without affecting mortality.^[33][34][35] The Cochrane review did not find any evidence that the radiation therapy had any long-termtoxic effects.^[33] While the authors caution that longer follow-up will be required before a definitive conclusion can be reached regarding long-term toxicity, they point out that ongoing technical improvements should further restrict radiation exposure in healthy tissues.^[33] They do recommend that comprehensive information on potential side effects is given to women who receive this treatment.^[33] The addition of radiation therapy to lumpectomy appears to reduce the risk of local recurrence to approximately 12%, of which approximately half will be DCIS and half will be invasive breast cancer; the risk of recurrence is 1% for women undergoing mastectomy.^[36]

There is no evidence that mastectomy decreases the risk of death over a lumpectomy.^[37] Mastectomy, however, may decrease the rate of the DCIS or invasive cancer occurring in the same location.^[7][37]

Mastectomies remain a common recommendation in those with persistent microscopic involvement of margins after local excision or with a diagnosis of DCIS and evidence of suspicious, diffuse microcalcifications.^[38]

Some institutions that have encountered high rates of recurrent invasive cancers after mastectomy for DCIS have endorsed routinesentinel node biopsy (SNB).^[39] However, research indicates that sentinel node biopsy has risks that outweigh the benefits for most women with DCIS.^[40] SNB should be considered with tissue diagnosis of high-risk DCIS (grade III with palpable mass or larger size on imaging) as well as in people undergoing mastectomy after a core or excisional biopsy diagnosis of DCIS.^[41][42]

With treatment, the prognosis is excellent, with greater than 97% long-term survival. If untreated, DCIS progresses to invasive cancer in roughly one-third of cases, usually in the same breast and quadrant as the earlier DCIS.^[43] About 2% of women who are diagnosed with this condition and treated died within 10 years.^[44] Biomarkers can identify which women who were initially diagnosed with DCIS are at high or low risk of subsequent invasive cancer.^[45][46]

DCIS is often detected with mammographies but can rarely be felt. With the increasing use of screening mammography, noninvasive cancers are more frequently diagnosed and now constitute 15% to 20% of all breast cancers.^[38]

Cases of DCIS have increased five-fold between 1983 and 2003 in the United States due to the introduction of screening mammography.^[44] In 2009 about 62,000 cases were diagnosed.^[44]

• Breast cancer

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