Ductal Carcinoma In Situ
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Ductal carcinoma ''in situ'' (DCIS), also known as intraductal carcinoma, is a pre-cancerous or non-invasive cancerous lesion of the
breast The breasts are two prominences located on the upper ventral region of the torso among humans and other primates. Both sexes develop breasts from the same embryology, embryological tissues. The relative size and development of the breasts is ...
. DCIS is classified as
Stage Stage, stages, or staging may refer to: Arts and media Acting * Stage (theatre), a space for the performance of theatrical productions * Theatre, a branch of the performing arts, often referred to as "the stage" * ''The Stage'', a weekly Brit ...
0. It rarely produces symptoms or a breast lump that can be felt, typically being detected through screening mammography. It has been diagnosed in a significant percentage of men (see
male breast cancer Male breast cancer (MBC) is a cancer in males that originates in their breasts. Males account for less than 1% of new breast cancers with about 20,000 new cases being diagnosed worldwide every year. Its incidence rates in males vs. females are, ...
). In DCIS, abnormal cells are found in the lining of one or more milk ducts in the breast. ''
In situ is a Latin phrase meaning 'in place' or 'on site', derived from ' ('in') and ' ( ablative of ''situs'', ). The term typically refers to the examination or occurrence of a process within its original context, without relocation. The term is use ...
'' 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 an invasive 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. 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 of
comedo A comedo (plural comedones) is a clogged hair follicle (pore) in the skin. Keratin (skin debris) combines with oil to block the follicle. A comedo can be open (blackhead) or closed by skin (whitehead) and occur with or without acne. The word ''com ...
histology; or, in the case of the
apocrine Apocrine () is a term used to classify the mode of secretion of exocrine glands. In apocrine secretion, secretory cells accumulate material at their apical ends, often forming blebs or "snouts", and this material then buds off from the cells ...
cell-based in situ carcinoma, apocrine ductal carcinoma ''in situ'', it may be classified according to the cell type forming the lesion. DCIS can be detected on
mammogram Mammography (also called mastography; DICOM modality: MG) is the process of using low-energy X-rays (usually around 30 kVp) to examine the human breast for diagnosis and screening. The goal of mammography is the early detection of breast cancer ...
s by examining tiny specks of calcium known as
microcalcification Microcalcifications are tiny Calculus (medicine), deposits of calcium salts that are too small to be felt but can be detected by medical imaging, imaging. They can be scattered throughout the mammary gland, or occur in clusters. Microcalcificat ...
s. Since suspicious groups of microcalcifications can appear even in the absence of DCIS, a
biopsy A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, an interventional radiologist, or an interventional cardiology, interventional cardiologist. The process involves the extraction of sampling (medicine), sample ...
may be necessary for diagnosis. About 20–30% of those who do not receive treatment develop
breast cancer Breast cancer is a cancer that develops from breast tissue. Signs of breast cancer may include a Breast lump, lump in the breast, a change in breast shape, dimpling of the skin, Milk-rejection sign, milk rejection, fluid coming from the nipp ...
. 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.


Terminology

Ductal carcinoma ''in situ'' (DCIS) literally means groups of "cancerous"
epithelial Epithelium or epithelial tissue is a thin, continuous, protective layer of cells with little extracellular matrix. An example is the epidermis, the outermost layer of the skin. Epithelial ( mesothelial) tissues line the outer surfaces of man ...
cells which remain in their normal location (''in situ'') within the ducts and lobules of the mammary gland. Clinically, DCIS is considered to be a premalignant (i.e. potentially
malignant Malignancy () is the tendency of a medical condition to become progressively worse; the term is most familiar as a characterization of cancer. A ''malignant'' tumor contrasts with a non-cancerous benign tumor, ''benign'' tumor in that a malig ...
) condition, because the biologically abnormal cells have not yet crossed the
basement membrane The basement membrane, also known as base membrane, is a thin, pliable sheet-like type of extracellular matrix that provides cell and tissue support and acts as a platform for complex signalling. The basement membrane sits between epithelial tis ...
to invade the surrounding tissue. When multiple lesions (known as "foci" of DCIS) are present in different quadrants of the breast, this is referred to as "multicentric" disease. For statistical purposes, DCIS is sometimes counted as a "cancer", but this is not always the case. When classified as a cancer, it is referred to as a "non-invasive" or "pre-invasive" form. It is described by the
National Cancer Institute The National Cancer Institute (NCI) coordinates the United States National Cancer Program and is part of the National Institutes of Health (NIH), which is one of eleven agencies that are part of the U.S. Department of Health and Human Services. ...
as a "noninvasive condition".


Signs and symptoms

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 at screening mammography. In a few cases, DCIS may cause: * A lump or thickening in or near the breast or under the
arm In human anatomy, the arm refers to the upper limb in common usage, although academically the term specifically means the upper arm between the glenohumeral joint (shoulder joint) and the elbow joint. The distal part of the upper limb between ...
* A change in the size or shape of the breast *
Nipple The nipple is a raised region of tissue on the surface of the breast from which, in lactating females, breast milk, milk from the mammary gland leaves the body through the lactiferous ducts to Breastfeeding, nurse an infant. The milk can flow th ...
discharge or nipple tenderness; the nipple may also be inverted, or pulled back into the breast * Ridges or pitting of the breast; the
skin Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation. Other animal coverings, such as the arthropod exoskeleton, have different ...
may look like the skin of an orange * A change in the way the skin of the breast,
areola The human areola (''areola mammae'', or ) is the pigmented area on the breast around the nipple. More generally, an areola is a small circular area on the Human body, body with a different histology from the surrounding Tissue (biology), tissue ...
, or nipple looks or feels such as warmth, swelling, redness or scaliness.


Causes

The specific causes of DCIS are still unknown. The risk factors for developing this condition are similar to those for invasive breast cancer. Some women are however more prone than others to developing DCIS. Women considered at higher risks are those who have a
family history Genealogy () is the study of families, family history, and the tracing of their lineages. Genealogists use oral interviews, historical records, genetic analysis, and other records to obtain information about a family and to demonstrate kins ...
of breast cancer, those who have had their periods at an early age or who have had a late
menopause Menopause, also known as the climacteric, is the time when Menstruation, menstrual periods permanently stop, marking the end of the Human reproduction, reproductive stage for the female human. It typically occurs between the ages of 45 and 5 ...
. Also, women who have never had
children A child () is a human being between the stages of childbirth, birth and puberty, or between the Development of the human body, developmental period of infancy and puberty. The term may also refer to an unborn human being. In English-speaking ...
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 Hyperplasia (from ancient Greek ὑπέρ ''huper'' 'over' + πλάσις ''plasis'' 'formation'), or hypergenesis, is an enlargement of an organ or tissue caused by an increase in the amount of Tissue (biology), organic tissue that results from ...
, as well as
radiation In physics, radiation is the emission or transmission of energy in the form of waves or particles through space or a material medium. This includes: * ''electromagnetic radiation'' consisting of photons, such as radio waves, microwaves, infr ...
exposure or exposure to certain
chemicals A chemical substance is a unique form of matter with constant chemical composition and characteristic properties. Chemical substances may take the form of a single element or chemical compounds. If two or more chemical substances can be combin ...
may also contribute in the development of the condition. 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. More definitive diagnosis is made by breast biopsy for
histopathology Histopathology (compound of three Greek words: 'tissue', 'suffering', and '' -logia'' 'study of') is the microscopic examination of tissue in order to study the manifestations of disease. Specifically, in clinical medicine, histopatholog ...
. File:Mammogram microcalcifications in carcinoma in situ, CC, details.png,
Mammogram Mammography (also called mastography; DICOM modality: MG) is the process of using low-energy X-rays (usually around 30 kVp) to examine the human breast for diagnosis and screening. The goal of mammography is the early detection of breast cancer ...
microcalcifications in ductal carcinoma ''in situ'' File:Histopathology of dystrophic microcalcifications in ductal carcinoma in situ.jpg, Histopathology of dystrophic microcalcifications in DCIS, H&E stain. File:Histopathologic architectural patterns of DCIS.png, Histopathologic architectural patterns of DCIS. File:Histopathology of high-grade DCIS.png, Histopathology of high-grade DCIS. H&E stain.
RBC =
red blood cell Red blood cells (RBCs), referred to as erythrocytes (, with -''cyte'' translated as 'cell' in modern usage) in academia and medical publishing, also known as red cells, erythroid cells, and rarely haematids, are the most common type of blood cel ...
. File:Histopathology of microinvasive ductal carcinoma in situ.png, DCIS with microinvasion, defined as focus of invasive cancer measuring up to 1.0 mm in size. File:Immunohistochemistry with calponin in ductal carcinoma in situ.jpg,
Immunohistochemistry Immunohistochemistry is a form of immunostaining. It involves the process of selectively identifying antigens in cells and tissue, by exploiting the principle of Antibody, antibodies binding specifically to antigens in biological tissues. Alber ...
for calponin in ductal carcinoma ''in situ'', highlighting myoepithelial cells around all tumor cells, thereby ruling out
invasive ductal carcinoma Invasive carcinoma of no special type (invasive carcinoma NST), invasive breast carcinoma of no special type (IBC-NST), invasive ductal carcinoma (IDC), infiltrating ductal carcinoma (IDC) or invasive ductal carcinoma, not otherwise specified (NOS ...
. File:Histopathology of ductal carcinoma in situ with comedo necrosis.jpg, Ductal carcinoma ''in situ'' with comedo necrosis spanning 30% of its diameter, which is generally regarded as the minimal size to classify it as comedo.Image by Mikael Häggström, MD.
- Reference for 30% being the most common definition of comedo necrosis by size:
-


Treatment

There are different opinions on the best treatment of DCIS. Surgical removal, with or without additional
radiation therapy Radiation therapy or radiotherapy (RT, RTx, or XRT) is a therapy, treatment using ionizing radiation, generally provided as part of treatment of cancer, cancer therapy to either kill or control the growth of malignancy, malignant cell (biology), ...
or
tamoxifen Tamoxifen, sold under the brand name Nolvadex among others, is a selective estrogen receptor modulator used to prevent breast cancer in women and men. It is also being studied for other types of cancer. It has been used for Albright syndrome ...
, is the recommended treatment for DCIS by the
National Cancer Institute The National Cancer Institute (NCI) coordinates the United States National Cancer Program and is part of the National Institutes of Health (NIH), which is one of eleven agencies that are part of the U.S. Department of Health and Human Services. ...
. Surgery may be either a breast-conserving
lumpectomy Lumpectomy (sometimes known as a tylectomy, partial mastectomy, breast segmental resection or breast wide local excision) is a surgical removal of a discrete portion or "lump" of breast tissue, usually in the treatment of a malignant tumor or bre ...
or a
mastectomy Mastectomy is the medical term for the surgical removal of one or both breasts, partially or completely. A mastectomy is usually carried out to treat breast cancer. In some cases, women believed to be at high risk of breast cancer choose to have ...
(complete or partial removal of the affected breast). If a lumpectomy is used it is often combined with radiation therapy. Tamoxifen may be used as hormonal therapy if the cells show
estrogen receptor Estrogen receptors (ERs) are proteins found in cell (biology), cells that function as receptor (biochemistry), receptors for the hormone estrogen (17β-estradiol). There are two main classes of ERs. The first includes the intracellular estrogen ...
positivity. Research shows that survival is the same with lumpectomy as it is with mastectomy, whether or not a woman has radiation after lumpectomy.
Chemotherapy Chemotherapy (often abbreviated chemo, sometimes CTX and CTx) is the type of cancer treatment that uses one or more anti-cancer drugs (list of chemotherapeutic agents, chemotherapeutic agents or alkylating agents) in a standard chemotherapy re ...
is not needed for DCIS since the disease is noninvasive.Ductal Carcinoma in Situ (DCIS)
,
Johns Hopkins Medicine The Johns Hopkins University School of Medicine (JHUSOM) is the medical school of Johns Hopkins University, a private research university in Baltimore, Maryland. Established in 1893 following the construction of the Johns Hopkins Hospital, the ...
While surgery reduces the risk of subsequent cancer, many people never develop cancer even without treatment and the associated side effects. There is no evidence comparing surgery with
watchful waiting Watchful waiting (also watch and wait or WAW) is an approach to a medical problem in which time is allowed to pass before medical intervention or therapy is used. During this time, repeated testing may be performed. Related terms include ''expe ...
and some feel watchful waiting may be a reasonable option in certain cases.


Radiation therapy

Use of
radiation therapy Radiation therapy or radiotherapy (RT, RTx, or XRT) is a therapy, treatment using ionizing radiation, generally provided as part of treatment of cancer, cancer therapy to either kill or control the growth of malignancy, malignant cell (biology), ...
after lumpectomy provides equivalent
survival rate Survival rate is a part of survival analysis. It is the proportion of people in a study or treatment group still alive at a given period of time after diagnosis. It is a method of describing prognosis in certain disease conditions, and can be use ...
s 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 review A systematic review is a scholarly synthesis of the evidence on a clearly presented topic using critical methods to identify, define and assess research on the topic. A systematic review extracts and interprets data from published studies on ...
s (including a
Cochrane review Cochrane is a British international charitable organisation formed to synthesize medical research findings to facilitate evidence-based choices about health interventions involving health professionals, patients and policy makers. It includes ...
) 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. The Cochrane review did not find any evidence that the radiation therapy had any long-term toxic effects. 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. They do recommend that comprehensive information on potential side effects is given to women who receive this treatment. 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.


Mastectomy

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


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). However, research indicates that sentinel node biopsy has risks that outweigh the benefits for most women with DCIS. 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.


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


Epidemiology

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


References


External links

{{Breast neoplasia Breast cancer