Ductal carcinoma
Encyclopedia
Breast cancer
Breast cancer is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas...
in women. It comes in two forms: invasive ductal carcinoma (IDC), an infiltrating, malignant
Malignant
Malignancy is the tendency of a medical condition, especially tumors, to become progressively worse and to potentially result in death. Malignancy in cancers is characterized by anaplasia, invasiveness, and metastasis...
and abnormal proliferation of neoplastic cells in the breast tissue, or ductal carcinoma in situ
In situ
In situ is a Latin phrase which translated literally as 'In position'. It is used in many different contexts.-Aerospace:In the aerospace industry, equipment on board aircraft must be tested in situ, or in place, to confirm everything functions properly as a system. Individually, each piece may...
(DCIS), a noninvasive, possibly malignant, neoplasm that is still confined to the milk ducts (lactiferous ducts), where breast cancer most often originates. Many doctors feel that DCIS is overdiagnosed and that many women who are treated for DCIS do not actually have cancer.
Invasive ductal carcinoma
Invasive ductal carcinoma (IDC) is the most common form of invasive breast cancer. It accounts for 55% of breast cancer incidence upon diagnosis, according to statistics from the United States in 2004. On a mammogramMammography
Mammography is the process of using low-energy-X-rays to examine the human breast and is used as a diagnostic and a screening tool....
, it is usually visualized as a mass with fine spikes radiating from the edges. On physical examination
Physical examination
Physical examination or clinical examination is the process by which a doctor investigates the body of a patient for signs of disease. It generally follows the taking of the medical history — an account of the symptoms as experienced by the patient...
, this lump usually feels much harder or firmer than benign breast lesions such as fibroadenoma
Fibroadenoma
Fibroadenomas of the breast, are lumps composed of fibrous and glandular tissue. Because breast cancer can also appear as a lump, doctors may recommend a tissue sample to rule out cancer in older patients...
. On microscopic examination, the cancerous cells invade and replace the surrounding normal tissues. IDC is divided in several histological
Histology
Histology is the study of the microscopic anatomy of cells and tissues of plants and animals. It is performed by examining cells and tissues commonly by sectioning and staining; followed by examination under a light microscope or electron microscope...
subtypes.
Prognosis for IDC
The prognosisPrognosis
Prognosis is a medical term to describe the likely outcome of an illness.When applied to large statistical populations, prognostic estimates can be very accurate: for example the statement "45% of patients with severe septic shock will die within 28 days" can be made with some confidence, because...
of IDC depends, in part, on its histological subtype. Mucinous, papillary, cribriform, and tubular carcinomas have longer survival, and lower recurrence rates. The prognosis of the most common form of IDC, called "IDC Not Otherwise Specified", is intermediate. Finally, some rare forms of breast cancer (e.g. sarcomatoid carcinoma, inflammatory carcinoma
Inflammatory breast cancer
Inflammatory breast cancer is an especially aggressive type of breast cancer that can occur in women of any age .It is called inflammatory because it frequently presents with symptoms resembling an inflammation...
) have a poor prognosis.
Regardless of the histological subtype, the prognosis of IDC depends also on tumor size, presence of cancer in the lymph nodes, histological grade
Grading (tumors)
In pathology, grading is a measure of the cell appearance in tumors and other neoplasms. Some pathology grading systems apply only to malignant neoplasms ; others apply also to benign neoplasms. The neoplastic grading is a measure of cell anaplasia in the sampled tumors arising from the...
, presence of cancer in small vessels (vascular invasion), expression of hormone receptors and of oncogenes like HER2/neu
HER2/neu
HER-2 also known as proto-oncogene Neu, receptor tyrosine-protein kinase erbB-2, CD340 or p185 is an enzyme that in humans is encoded by the ERBB2 gene. Over expression of this gene is correlated with higher aggressiveness in breast cancers...
.
These parameters can be entered into models that provide a statistical probability of systemic spread. The probability of systemic spread is a key factor in determining whether radiation and chemotherapy are worthwhile. The individual parameters are important also because they can predict how well a cancer will respond to specific chemotherapy agents.
Overall, the 5-year survival rate of invasive ductal carcinoma was approximately 85% in 2003.
Tumor size
Tumors under 1 cm in diameter are unlikely to spread systemically. Tumors are staged by size.| Diameter | Tumor size staging number |
|---|---|
| 0–5 mm | T1a |
| 5–10 mm | T1b |
| 10–20 mm | T1c |
| 20-50mm | T2 |
| >50 mm | T3 |
| Tumor involves skin or chest wall | T4 |
Lymph node involvement
Absence of cancer cells in the lymph nodes is a good indication that the cancer has not spread systemically. Presence of cancer in the lymph nodes indicates the cancer may have spread. In studies, some women have had presence of cancer in the lymph nodes, were not treated with chemotherapy, and still did not have a systemic spread. Therefore, lymph node involvement is not a positive predictor of spread.| Lymph node status | Lymph node involvement grade |
|---|---|
| No involved nodes | N0 |
| Involved node or nodes | N1 |
| Involved nodes that are fixed to one another | N2 |
Clinical staging
Tumor size staging and node involvement staging can be combined into a single clinical staging number.| Tumor size staging | Node involvement staging | Clinical stage |
|---|---|---|
| T1 | N0 | I |
| T1 | N1 | IIA |
| T2 | N0 | IIA |
| T2 | N1 | IIB |
| T3 | N0 | IIB |
| T1-T2 | N2 | IIIA |
| T3 | N1 | IIIA |
| T3 | N2 | IIIA |
| T4 | N0-N2 | IIIB |
Histologic appearance
The appearance of cancer cells under a microscope is another predictor of systemic spread. The more different the cancer cells look compared to normal duct cells, the greater the risk of systemic spread. There are three characteristics that differentiate cancer cells from normal cells.- Tendency to form tubular structures
- Nuclear size, shape, and staining intensity
- Mitotic rate - Rate of cell division
The histologic appearance of cancer cells can be scored on these three parameters on a scale from one to three. The sum of these grades is a number between 3 and 9. The score is called a Bloom Richardson Grade (BR) and is expressed [sum of the grades]/9. For example, cells that were graded 2 on all three parameters would result in a BR score of 6/9.
A score of 5 and under is considered Low. 6 to 7 is considered Intermediate. 8 to 9 is considered High.
Vascular invasion
The presence of cancer cell in small blood vessels is called vascular invasion. The presence of vascular invasion increases the probability of systemic spread.DNA analysis
DNA analysis indicates the amount of DNA in cancer cells and how fast the cancer is growing.Cells with the normal amount of DNA are called diploid. Cells with too much or too little DNA are called aneuploid. Aneuploid cells are more likely to spread than diploid cells.
DNA testings indicates the rate of growth by determining the number of cells in the synthetic phase (S Phase). An S Phase > 10% means a higher chance of spreading.
The results of DNA testing are considered less reliable predictors of spread than size, histology, and lymph node involvement.
Treatment options for IDC
Treatment of IDC depends on the size of the mass (size of the tumor measured in its longest direction):- <4 cm mass: surgery to remove the main tumor mass and to sample the lymph nodes in the axilla. The stageCancer stagingThe stage of a cancer is a description of the extent the cancer has spread. The stage often takes into account the size of a tumor, how deeply it has penetrated, whether it has invaded adjacent organs, how many lymph nodes it has metastasized to , and whether it has spread to distant organs...
of the tumor is ascertained after this first surgery. Adjuvant therapy (i.e. treatment after surgery) may include a combination of chemotherapyChemotherapyChemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
, radiotherapy, hormonal therapy (e.g. tamoxifenTamoxifenTamoxifen is an antagonist of the estrogen receptor in breast tissue via its active metabolite, hydroxytamoxifen. In other tissues such as the endometrium, it behaves as an agonist, hence tamoxifen may be characterized as a mixed agonist/antagonist...
) and/or targeted therapy (e.g. trastuzumabTrastuzumabTrastuzumab is a monoclonal antibody that interferes with the HER2/neu receptor.The HER receptors are proteins that are embedded in the cell membrane and communicate molecular signals from outside the cell to inside the cell, and turn genes on and off...
). More surgery is occasionally needed to complete the removal of the initial tumor or to remove recurrences. - 4 cm or larger mass: modified (a less aggressive form of radical mastectomy) radical mastectomy (because any malignant mass in excess of 4 cm in size exceeds the criteria for a lumpectomy) along with sampling of the lymph nodes in the axilla.
The treatment options offered to an individual patient are determined by the form, stage and location of the cancer, and also by the age, history of prior disease and general health of the patient. Not all patients are treated the same way.
Ductal carcinoma in situ (intraductal carcinoma)
Ductal carcinoma in situ (DCIS, also known as intraductal carcinoma) is the most common type of noninvasive breast cancer or pre-cancer in women. Ductal carcinoma refers to the development of cancer cells within the milk ductsMammary gland
A mammary gland is an organ in mammals that produces milk to feed young offspring. Mammals get their name from the word "mammary". In ruminants such as cows, goats, and deer, the mammary glands are contained in their udders...
of the breast. In situ
In situ
In situ is a Latin phrase which translated literally as 'In position'. It is used in many different contexts.-Aerospace:In the aerospace industry, equipment on board aircraft must be tested in situ, or in place, to confirm everything functions properly as a system. Individually, each piece may...
means "in place" and refers to the fact that the cancer has not moved out of the duct and into any surrounding tissue.
DCIS has been referred to as "stage zero breast cancer". Experts disagree on whether it should even be called "cancer" at all. It is known to be a risk factor
Risk factor
In epidemiology, a risk factor is a variable associated with an increased risk of disease or infection. Sometimes, determinant is also used, being a variable associated with either increased or decreased risk.-Correlation vs causation:...
for invasive ("real") breast cancer, and in a small fraction of cases it is a precancerous condition that may eventually transform into invasive breast cancer. DCIS is not traditionally regarded as being harmful in itself; however, there is evidence of metastases in up to 2% of cases of DCIS. The use of the term carcinoma in the official name is misleading (the term carcinoma is only supposed to be used for invasive cancers) and frightening to women diagnosed with DCIS, and at least one expert responsible for its naming now regrets the choice. In 2009, the US NIH said that DCIS should be renamed to be more accurate and less needlessly frightening to patients, just like what was previously called "stage zero cervical cancer" is now more accurately named cervical intraepithelial neoplasia
Cervical intraepithelial neoplasia
Cervical intraepithelial neoplasia , also known as cervical dysplasia and cervical interstitial neoplasia, is the potentially premalignant transformation and abnormal growth of squamous cells on the surface of the cervix. CIN is not cancer, and is usually curable...
. They recommended high-grade dysplasia
Dysplasia
Dysplasia , is a term used in pathology to refer to an abnormality of development. This generally consists of an expansion of immature cells, with a corresponding decrease in the number and location of mature cells. Dysplasia is often indicative of an early neoplastic process...
as a possible new name for DCIS.
DCIS almost never produces symptoms or a lump that can be felt, so it is almost always found through screening mammography. As screening mammography has become more widespread, DCIS has become one of the most commonly diagnosed breast conditions, now accounting for 20% of breast cancers and pre-cancers that are detected through screening mammography. DCIS is usually seen on a mammogram as very small specks of calcium known as microcalcification
Microcalcification
Microcalcifications are tiny specks of mineral deposits , that can be scattered throughout the mammary gland, or occur in clusters. When found on a mammogram, a radiologist will then decide whether the specks are of concern - usually, this is not the case...
s. However, not all microcalcifications indicate the presence of DCIS, which must be confirmed by biopsy.
Even without treatment, a majority of women with DCIS will not develop invasive breast cancer from the DCIS. However, surgical excision, aimed at excising all of the abnormal duct elements, is a common treatment, and radiation after surgery further reduces the risk that the DCIS will recur.
Treatment options for DCIS
DCIS patients have two surgery strategy choices: They are lumpectomyLumpectomy
Lumpectomy is a common surgical procedure designed to remove a discrete lump, usually a benign tumor or breast cancer, from an affected man or woman's breast...
(most commonly followed by radiation therapy) or mastectomy
Mastectomy
Mastectomy is the medical term for the surgical removal of one or both breasts, partially or completely. Mastectomy is usually done to treat breast cancer; in some cases, women and some men believed to be at high risk of breast cancer have the operation prophylactically, that is, to prevent cancer...
. The survival rate is equally high for both treatments, 96 percent or higher.
Women also have the option of rejecting surgery. The survival rate here is unknown, but since a majority of DCIS never transforms into invasive breast cancer, it is not small. Women who reject surgery tend to be older or have other, serious health problems, which further complicates comparisons.
Biomarkers can identify which women who were initially diagnosed with DCIS are at high or low risk of subsequent invasive cancer.
Adjunct radiotherapy after lumpectomy offers equivalent survival to mastectomy, although there is a slightly higher risk of recurrence of DCIS or breast cancer. The addition of radiation therapy to lumpectomy reduces the risk of local recurrence to approximately 12 percent, of which approximately half will be DCIS and half will be breast cancer; the risk of recurrence is 1 percent for women undergoing mastectomy. In addition, radiation therapy
Radiation therapy
Radiation therapy , radiation oncology, or radiotherapy , sometimes abbreviated to XRT or DXT, is the medical use of ionizing radiation, generally as part of cancer treatment to control malignant cells.Radiation therapy is commonly applied to the cancerous tumor because of its ability to control...
may reduce recurrence among patients with DCIS getting breast-conserving surgery (lumpectomy) as compared to breast-conserving surgery alone according to a systematic review
Systematic review
A systematic review is a literature review focused on a research question that tries to identify, appraise, select and synthesize all high quality research evidence relevant to that question. Systematic reviews of high-quality randomized controlled trials are crucial to evidence-based medicine...
. Patients who received breast-conserving surgery plus radiation therapy had a lower DCIS recurrence rate than patients who received breast conserving surgery alone. The use of radiation therapy did not have an effect on mortality.
Black women with DCIS have higher risks of local recurrence of DCIS or breast cancer than white women. Extensive DCIS of high grade, large size, and resected with minimal surgical margins, even with radiotherapy, also have a higher risk of recurrence.
Because of the higher risk of recurrence, mastectomy
Mastectomy
Mastectomy is the medical term for the surgical removal of one or both breasts, partially or completely. Mastectomy is usually done to treat breast cancer; in some cases, women and some men believed to be at high risk of breast cancer have the operation prophylactically, that is, to prevent cancer...
may be the preferred treatment for some women or in certain instances e.g. if:
- DCIS is "multi-focal" (present in two or more areas of the breast).
- The DCIS tumor is relatively large or of high grade.
- Failure to achieve adequate margins on attempted lumpectomy.
- The breast has previously received radiationRadiationIn physics, radiation is a process in which energetic particles or energetic waves travel through a medium or space. There are two distinct types of radiation; ionizing and non-ionizing...
treatment. - The patient has had sclerodermaSclerodermaSystemic sclerosis or systemic scleroderma is a systemic autoimmune disease or systemic connective tissue disease that is a subtype of scleroderma.-Skin symptoms:...
or another disease of the connective tissue, which can complicate radiation treatment. - The patient lives in an area where radiation treatment is inaccessible or inconvenient.
- The patient is under the age of 40.
A system for analyzing the suitability of DCIS patients for the options of breast conservation without radiation, breast conservation with radiation, or mastectomy is called the VanNuys Prognostic Scoring Index (VNPI). This VNPI analyzes DCIS features in terms of size, grade, surgical margins, and patient age and assigns "scores" to favorable features.
Tamoxifen or another hormonal therapy is recommended for some women with estrogen-receptor positive DCIS to help prevent breast cancer. Hormonal therapy further decreases the risk of recurrence of DCIS or the development of invasive breast cancer. However, hormone treatment increases the risk of endometrial cancer, severe circulatory problems, or stroke. In addition, hot flashes, vaginal dryness, abnormal vaginal bleeding, and a possibility of premature menopause are common for pre—menopausal women who start treatment.
Unlike women with invasive breast cancer, women with DCIS do not undergo chemotherapy and have traditionally not been advised to have their lymph nodes tested or removed. Some institutional series reporting significant rates of recurrent invasive cancers after mastectomy for DCIS have recently endorsed routine sentinel node biopsy (SNB) in these patients, while others have concluded it be reserved for selected patients. Most agree that 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 patients undergoing mastectomy after a core or excisional biopsy diagnosis of DCIS. Experts are not sure whether all women with DCIS would eventually develop invasive breast cancer if they live long enough without undergoing treatment.
What happens if DCIS is not treated?
According to the NIH Consensus Conference, many DCIS lesions will never become breast cancer, and some will disappear without treatment. If DCIS is allowed to go untreated, the natural course or natural historyNatural history of disease
The natural history of disease refers to a description of the uninterrupted progression of a disease in an individual from the moment of exposure to causal agents until recovery or death. Knowledge of the natural history of disease ranks alongside causal understanding in importance for disease...
varies according to the grade of the DCIS.
Unless treated, approximately 60 percent of low-grade DCIS lesions will become invasive at 40 years follow-up—long after many of the diagnosed women have died from other causes. The remaining 40 percent of low-grade DCIS lesions will remain harmless.
High-grade DCIS lesions that have been inadequately resected and not given radiotherapy have a 50 percent risk of becoming invasive breast cancer within seven years. Approximately half of low-grade DCIS detected at screening will represent overdiagnosis, but overdiagnosis of high-grade DCIS is rare.
The natural history of intermediate-grade DCIS is difficult to predict. Approximately one-third of malignant calcification clusters detected at screening mammography already have an invasive focus.