Ductal carcinoma in situ

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Breast cancer in situ
Other names: Intraductal carcinoma, ductal intraepithelial neoplasia[1]
Lobules and ducts of the breast.jpg
Ducts of the mammary gland, the location of ductal carcinoma
SpecialtyOncology
SymptomsNone, nipple discharge, rash at the nipple, breast lump[1]
TypesComedo, cribriform, micropapillary, papillary, solid[2]
Risk factorsOlder age, family history, not having children, genetics[2][3]
Diagnostic methodMammogram, biopsy[4]
Differential diagnosisInvasive breast cancer[3]
TreatmentSurgery, radiation therapy, hormone therapy[1]
PrognosisGood[5]
Frequency>60,000 women/yr (USA)[5]

Ductal carcinoma in situ (DCIS), also known as intraductal carcinoma, is a pre-cancerous or non-invasive cancer of the breast.[6][7] It rarely produces symptoms; typically being detected by screening mammography, though occasionally nipple discharge, rash at the nipple, or a breast lump may occur.[1][2] About 20% of cases develop into invasive breast cancer; though, this may be as high as 60% without treatment during prolonged follow-up.[8][9]

Risk factors include older age, family history, not having children, and the genetic changes BRCA1 and BRCA2.[2][3] The abnormal cells only occur within breast ducts; though this may involve a large area of the breast.[10] Diagnosis is generally suspected when a mammogram finds calcification; with tissue biopsy used for confirmation.[4][2] It is classified as stage 0 cancer and can vary from low-grade to high-grade.[1]

Treatment is generally by surgery, either a lumpectomy or a mastectomy.[1] Other treatments that may be used include radiation therapy and hormone therapy.[1] With treatment life expectancy is typically normal; though, over 20 years the risk of death from breast cancer is three times greater at about 3%.[3]

DCIS is diagnosed in more than 60,000 women in the United States and 7,000 in the United Kingdom per year.[5][1] It represents about 25% of breast cancer in women and about 10% of male breast cancer.[5][11] Rates have increased from less than 5% before screening programs launched.[3] There is disagreement on its status as cancer; with some bodies include DCIS when calculating breast cancer statistics, while others do not.[12]

Terminology

Ductal carcinoma in situ (DCIS) literally means groups of "cancerous" epithelial cells which remained in their normal location (in situ) within the ducts and lobules of the mammary gland.[13] Clinically, it is considered a premalignant (i.e. potentially malignant) condition,[14] because the biologically abnormal cells have not yet crossed the basement membrane to invade the surrounding tissue.[13][15] When multiple lesions (known as "foci" of DCIS) are present in different quadrants of the breast, this is referred to as "multicentric" disease.[16]

Some count DCIS as a "cancer", whereas others do not.[17][18] When classified as a cancer, it is referred to as a non-invasive or pre-invasive form.[13][19] The National Cancer Institute describes it as a "noninvasive condition".[17]

Signs and symptoms

A drawing of ductal carcinoma in situ in the anatomical context of the whole breast
Drawing of a breast duct containing ductal carcinoma in situ.

Most women who develop DCIS do not experience any symptoms. The majority of cases (80-85%) are detected through screening mammography. The first symptoms may appear if the cancer advances.

In a few cases, DCIS may cause:

  • A lump or thickening in or near the breast or under the arm
  • 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; the skin may look like the skin of an orange
  • A change in the way the skin of the breast, areola, or nipple looks or feels[20] such as warmth, swelling, redness or scaliness.[21]

Causes

The specific causes of DCIS are still unknown. The risk factors for developing this condition are similar to those for invasive breast cancer.[22]

Some women are however more prone than others to developing DCIS. Women considered at higher risks are those who have a family history of breast cancer, those who have had their periods at an early age or who have had a late menopause. Also, women who have never had children 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), atypical hyperplasia, as well as radiation exposure or exposure to certain chemicals may also contribute in the development of the condition.[23] Nonetheless, the risk of developing noninvasive cancer increases with age and it is higher in women older than 45 years.

Diagnosis

80% of cases in the United States are detected by mammography screening.[24] More definitive diagnosis is made by breast biopsy for histopathology.

It is classified according to the architectural pattern of the cells (solid, cribriform, papillary, and micropapillary), tumor grade (high, intermediate, and low grade), the presence or absence of comedo histology,[16] or the cell type forming the lesion in the case of the apocrine cell-based in situ carcinoma, apocrine ductal carcinoma in situ.[25]

Treatment

There are different opinions on the best treatment.[30] Surgical removal, with or without additional radiation therapy or tamoxifen, is the recommended by the National Cancer Institute.[31] Surgery may be either a breast-conserving lumpectomy or a mastectomy (complete or partial removal of the affected breast).[32] A lumpectomy is often combined with radiation therapy.[17] Tamoxifen may be used as hormonal therapy if the cells show estrogen receptor positivity.[17] Survival is the same with lumpectomy as it is with mastectomy, whether or not a woman has radiation after lumpectomy.[33] Chemotherapy is not needed since the disease is noninvasive.[34]

While surgery reduces the risk of subsequent cancer, many people never develop cancer even without treatment and the associated side effects.[32] There is no evidence comparing surgery with watchful waiting and some feel watchful waiting may be a reasonable option in certain cases.[32]

Mastectomy

There is no evidence that mastectomy decreases the risk of death over a lumpectomy.[35] Mastectomy, however, may decrease the rate of the DCIS or invasive cancer occurring in the same location.[36] [35]

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.[37]

Radiation

Radiation therapy after lumpectomy provides equivalent survival 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 a Cochrane 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.[38][39][40] The Cochrane review did not find any evidence that the radiation therapy had any long-term toxic effects.[38] 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.[38] They do recommend that comprehensive information on potential side effects is given to women who receive this treatment.[38] 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.[41]

Sentinel node biopsy

Some institutions that have encountered high rates of recurrent invasive cancers after mastectomy for DCIS have endorsed routine sentinel node biopsy (SNB).[42] However, research indicates that sentinel node biopsy has risks that outweigh the benefits for most women with DCIS.[43] 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.[44][45]

Prognosis

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.[46] About 2% of women who are diagnosed with this condition and treated died within 10 years.[47] Biomarkers can identify which women who were initially diagnosed with DCIS are at high or low risk of subsequent invasive cancer.[48][49]

Epidemiology

Histopathologic types of breast cancer, with relative incidences and prognoses. "Ductal carcinoma in situ" is near top.

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.[37]

Cases have increased five-fold between 1983 and 2003 in the United States due to the introduction of screening mammography.[47] In 2009 about 62,000 cases were diagnosed.[47]

References

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  29. Image by Mikael Häggström, MD.
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