Table of Contents
You may read everything concerning causes, risk factors, symptoms and special types of mammary carcinoma in the following article: Mammary Carcinoma I – Causes, Classification and Symptoms.
Diagnosis of Mammary Carcinoma
Patient history and clinical examinations in cases of mammary carcinoma
It is important to ask the patient targeted questions regarding the aforementioned symptoms as well as individual risk factors. This is followed by an examination with the patient’s upper body unclothed and her arms down as well as with her arms raised up whereby close attention should also be paid to the aforementioned symptoms (changes in the size of the breast, differences between both sides, skin retraction, etc.).
Palpation should be done after the end of menstruation while the patient is sitting up and lying down. Hereby, the breast is divided into four quadrants and is palpated against the thorax wall, checking for nipple discharge when lightly pressing on the mammary gland. Furthermore, it is important to palpate the supraclavicular and axillary lymph nodes.
In cases where skin retraction is visible, it is important to find out if it increases when the arms are elevated. Another diagnostic tool to be used is the Jackson test during which the skin is compressed over the palpable densification. If the skin retraction increases, the test is positive.
For the early detection of breast cancer, women over the age of 30 should be offered annual clinical exams.
Patients should be encouraged to regularly perform breast self-exams and palpation as not all carcinoma may be detected via mammography. The majority of carcinoma (> 70 percent) are detected by the women themselves, which is why breast self-exam is an important method of early detection. Self-exam alone, however, may not reduce the mortality rate.
Diagnostic tools for mammary carcinoma
Mammography is the gold standard of the instrument-based examination of the breast for the early detection of mammary carcinoma. It is being done every two years as part of a screening program for women between the ages of 50 and 70 or annually if women have a family risk factor (starting at age 30.).
A mammography should also be done from the age of 35 on in cases where irregularities were found during the clinical examinations, whereas women under the age of 35 should have a sonography.
In order to obtain conclusive images and to keep the radiation dose as low as possible, it is necessary to compress the breast between object table and Plexiglas compression plate, which may be painful.
Mammography is a specific type of low-dose x-ray imaging in which radiopaque structures such as carcinoma, calcifications or fibroadenomas create shadows but appear light on the scan whereas fatty tissue appears dark.
While benign tumors mostly appear homogenous, smoothly outlined and dense, the following criteria are signs of malignant findings:
- Asymmetric focal findings with unsharp delineation
- Inhomogenous band- and mesh-like shadows
- Star-shaped thickening with spicules
- Polymorphic clustered microcalcifications (pointing toward DCIS!)
- Surrounding tissue: retraction phenomenon
- Outlined thickening/retraction (skin, mammillary gland)
Mammography has a sensitivity of between 85 to 90 percent, depending on the tissue density: The fattier the tissue, the better the sensitivity. The specificity, however, is very limited.
Mammography findings are classified according to BI-RADS (Breast Imaging-Reporting and Data System):
|BI-RADS||Diagnosis/Findings||Procedure||Risk of carcinoma|
|0||Imaging has not been concluded||Further clarification is necessary||–|
|1||Unremarkable findings||Normal care||0 %|
|2||Benign findings||Normal care||0 %|
|3||Unclear, probably benign findings||Requiring follow-up (after six months)||< 2 %|
|4||Suspect findings||Histological clarification||2 – 90 %|
|5||Suspecting carcinoma||Histological clarification||> 90 %|
|6||Histolically confirmed carcinoma||–||100 %|
Other imaging diagnostic tools
In addition to the aforementioned methods, the following tests may be done:
- Most important complimentary screening in addition to mammography
- Benefit: no radiation exposure
- Disadvantage: highly operator-dependent, not suited for screening
- Criteria of malignancy: echo-poor, dorsal sound damping, unsharp ragged border contours, inhomogeneous, rarely with lateral shadow, cannot be compressed, surrounding structures disturbed
- Imaging of the milk-producing ducts using contrast agent injections followed by x-rays with mammillary gland secretion
- Pathological findings: caliber fluctuations in the milk ducts, discontinue contrast agent.
- Conclusive findings are only possible with contrast agents.
- Benefit: high soft-tissue contrast, very high sensitivity.
- Disadvantage: low specificity, no detection of microcalcifications.
- Indication: differential diagnosis: scar tissue/recurrence after surgery for mammary carcinoma, primary tumor screening in cases of axillary lymph node involvement, high-risk female patients, condition following reconstructive surgery
If metastases are suspected, pretherapeutic staging to include chest x-rays, liver sonography as well as skeletal scintigraphy should be pursued.
Biopsies in cases of mammary carcinoma
In order to further plan how to proceed and treat a patient if mammary carcinoma is suspected, it is necessary to histologically confirm the diagnosis. For this purpose, tissue samples are collected from the suspicious area via minimally invasive procedures and subsequently examined microscopically. The following procedures may be used:
1. Sonographically controlled punch biopsy.
During an interventional punch biopsy which is, preferably, controlled sonographically, no less than three samples using a 14G core needle should be removed.
2. Stereotactically controlled vacuum biopsy (or MIBB: minimally invasive breast biopsy) under mammographic control, in cases of, among others, microcalcifications.
3. Stereotactic excisional biopsy (or ABBI: advanced breast biopsy instrumentation), en bloc resection, especially in cases of microcalcifications.
Histology in cases of mammary carcinoma
After the tumor has been biopsied, it can be classified according to the TNM classification. The table in the first part of the article regarding mammary carcinoma will provide you with an overview.
Immunohistochemical staining of tumor cells is used in the diagnosis of tumors and may determine therapy. Hereby, the hormone receptors (estrogen, progesterone, steroid hormones) as well as the growth factor receptors (HER2/neu) play a role:
If more than ten percent of the tumor cells stain positive for estrogen and/or progesterone receptors (ER/PR), the mammary carcinoma is hormone-receptor-positive. This means that it is suitable for endocrine therapy and has, in addition, a better prognosis.
In cases of an invasive mammary carcinoma, HER2/neu is overexpressed, which is referred to as HER2-positive. This status of overexpression indicates the direction of therapy: In cases of HER2/neu positive 3+, patients are treated with trastuzumab, an HER2 antibody.
In cases of HER2/neu postive 2+, the FISH test has to be performed to check for HER2 gene amplification, which would indicate a more probable success of therapy.
In cases of HER2 1+ or HER2 0, a response to therapy is not expected as there is no overexpression.
Symptoms similar to mammary carcinoma
The general goal is to differentiate between, benign and malignant changes. Benign mammary tumors include, for instance, fibroadenomas or lipoms. Cystic changes, papillomas or mastopathy must be ruled out with regard to differential diagnoses. Especially with symptoms of inflammatory mammary carcinoma, Mastitis non-puerpalis must be considered as differential diagnosis.
Therapy of Mammary Carcinoma
Neoadjuvant treatment of mammary carcinoma
In order to shrink large tumors (T4, T3), treatment may begin before surgery with chemotherapy or endocrine therapy.
Surgical treatment of mammary carcinoma
Surgical treatment of mammary carcinoma includes the option to either radically remove the breast or to opt for breast-conserving therapy with the same goal, namely to remove the tumor as well as affected regional lymph nodes (in sano tumor resection, R0 status). The fact that this surgery is so radical does not, however, correlate with the chances of recovery, which is why the ground rule „as little as necessary“ should be applied.
Breast-conserving treatment of mammary carcinoma
Today’s standard method of surgical treatment is breast-conserving treatment (BCT) followed by radiation therapy of the remaining breast tissue. The prerequisite is that the tumor has not yet infiltrated the surrounding tissue and that there is a favorable ratio between the size of the tumor and the volume of the breast, which is the case in approximately 70 percent of female patients.
- Lumpectomy: It usually involves an incision the shape of an oval above the tumor, removal of the tumor and the removal of healthy tissue the size of one centimeter as a secure border on all sides. In some cases, the removal of the nipple may be necessary as well. The removal of the axillary lymph nodes is done with a second incision.
- Quadrantectomy: Removal of the quadrant of the breast where the tumor is located as well as the axillary lymph nodes.
Mastectomy in cases of mammary carcinoma
In cases where the size or the extent, respectively, of the tumor, in cases of tumor multicentricity or if the patient is contraindicated for post-surgery radiation, BCT will not be an option. In those situations – or if the patient does not desire this type of procedure – a modified radical mastectomy (Ablatio mammae with axillary revision) is performed.
During this procedure, the breast, the axillary lymph nodes as well as the pectoral fascia are removed, while the pectoral musculature (as opposed to a Halsted radical mastectomy) is preserved. In cases of inflammatory mammary carcinomas, there is an indication for a mastectomy as well.
The female patients must be educated on the option of breast reconstruction, which may take place simultaneously or after a latent period of at least six months. Suitable materials include heterologous implants or autologous tissue. Autologous tissue allows for the following flap technique reconstructions:
- Thoraco-epigastric flap reconstruction
- Latissimus dorsi flap reconstruction
- (Transverse) Rectus abdominis (myocutaneous) flap reconstruction (TRAM)
In order to determine a patient’s nodal status, it is necessary to perform a lymphonodectomy.
An axillary dissection is used for the removal of axillary lymph node fat tissue (level I and II) and is performed during BCT procedures as well as during mastectomies. A minimum of ten lymph nodes must be removed and examined. Caused by the removal of the lymph nodes, there is an increased risk of lymphedema.
If the tumor is less than three centimeters in size, the axillary lymph nodes have not been affected and if there are no contra indications (i.e. a multifocal, multicentric, metastasizing or inflammatory mammary carcinoma, Paget disease), the sentinel lymph node should be removed.
During this procedure, the lymph node that is attacked by the tumor cells first because of the lymph flow (sentinel/guardian lymph node), is marked via injection of peritumoral subdermal dye or radionuclide.
If this lymph node is free of tumor (sentinel negative), the removal of the axillary lymph node is not necessary resulting in reduced shoulder-arm morbidity.
As a rule for SNL positive female patients (macrometastases), axillary dissection with removal of a minimum of ten lymph nodes from levels I and II is indicated.
Adjuvant therapy of mammary carcinoma
Adjuvant therapy takes place after the resection of the tumor with the goal to reduce the risk of a local recurrence and to eliminate potential tumor cells in the body. This can be systemically achieved via local radiation, chemotherapy, or via endocrine or monoclonal antibody therapy, respectively.
Adjuvant postoperative radiation (50 – 60 Gy) following BCT is an obligatory measure in order to reduce the risk of local recurrence. Following a mastectomy involving large tumors (pT3, pT4), in cases of skin infiltration or extensive lymphangiosis and if more than three axillary lymph nodes are affected, adjuvant radiation therapy is indicated.
Chemotherapy is indicated if there is an increased risk of recurrence and it should begin one to two weeks following surgery. The most frequent medications used are a combination of cytostatic drugs for which regular recommendations are established in guidelines and during the St. Gallen expert consensus conference. Anthracycline and taxane are currently considered to be the most effective chemotherapy drugs.
In cases of HER2/neu-positive cancers, it is imperative to administer the monoclonal antibody trastuzumab for one year in addition to chemotherapy (see above).
For ER-/PR-positive female patients (see above), endocrine therapy is indicated. The goal is estrogen deprivation in order to decrease the growth of carcinoma cells or even stop it, respectively. The standard medication being used is tamoxifen (20 mg/day, oral). Another option for premenopausal patients is the administration of GnRH analogues in order to suppress ovarian function. Aromatase inhibitors are indicated for postmenopausal patients.
There are the following therapy schemes:
- Taking tamoxifen for five years
- Taking aromatase inhibitors for five years
- Taking tamoxifen for two to three years followed by taking aromatase inhibitors for a total therapy duration of five years
- Taking aromatase inhibitors followed by taking tamoxifen for a total therapy duration of five years
- Taking tamoxifen for five years followed by taking aromatase inhibitors for five years
Follow-up, Prognosis and Prevention of Mammary Carcinoma
Follow-up care in cases of mammary carcinoma
After locoregional primary therapy, follow-up is recommended. The gathering of the patient’s history, clinical and gynecological examinations as well as instrument-based diagnosis (sonography, mammography) should be done.
Furthermore, there should be follow-up examinations, every three months during the first three years, every six months during the fourth and fifth year, and annually after the sixth year. After a mammary carcinoma, the risk of contralateral breast cancer is two to five times higher which is why there should be an annual instrument-based check-up in that area as well.
Prognosis for mammary carcinoma
Basically, primary mammary carcinoma can be cured which is why therapy is curative. The chances of recovery depend on the tumor stage at the time the carcinoma is discovered. The earlier it is detected and treated, the better the prognosis.
In cases of remote metastases (in five percent of female patients when they are first diagnosed and in 30 percent of patients during the progression of the disease), therapy will take a palliative course as healing is no longer possible. The median survival time is approximately two years, the five-year survival rate is between five and ten percent, approximately.
Preventing mammary carcinoma
In order to prevent mammary carcinoma (primary prevention), the following options are available:
- In cases of hereditary mammary carcinoma, a bilateral mastectomy with a risk reduction of 90 percent and/or a bilateral adnexectomy with a risk reduction of 50 percent should be considered.
- In cases where the patient is at increased risk, drug therapy with tamoxifen, strictly according to indication, may be an option.
Early detection screenings serve as secondary prevention (see above).
The answers are below the references.
1. During a breast self-exam, a 53-year-old female patient noticed a palpable resistance in the left mamma. She presents at her gynecologist’s office who, during the clinical examination, detects a palpable tumor, 1.2 cm in size. The tumor also shows up in sonography imaging. Which diagnostic step should be next?
- MRT examination of the mamma
- Stereotactically controlled vacuum biopsy
- CT-examination of the mamma
2. Which of the following mammography findings is the least likely indicator for a malignant tumor?
- Asymmetrical focal findings
- Inhomogeneous, band-like shadows
- Star-shaped thickening with spicules
- Homogeneous, dense findings, smoothly outlined
- Polymorphous, clustered microcalcifications
3. Which of the aforementioned therapy options are not suitable for treating a mammary carcinoma?
- Modified radical mastectomy
- Systemic chemotherapy
- Antibody therapy