Breast cancer: causes, treatment, prognosis

Overview

Breast cancer (breast cancer) is one of the most common malignant tumors in women. The risk of developing breast cancer once in a lifetime is estimated to be around 12% in Germany. Every year in Germany about 70,000 women are diagnosed with breast cancer. In rare cases, even men may be affected by the disease.

The reasons why breast cancer develops are not yet fully understood. However, several risk factors for the development of a malignant tumor disease of the mammary gland could be detected. These include:

  • advanced age
  • big boobs
  • some benign breast changes (called mastopathy)
  • lack of exercise
  • heavy alcohol consumption
  • Smoke
  • hormonal influences
  • childlessness
  • familial predisposition

The earlier the cancer is detected, the better

Early diagnosis is crucial for the course of therapy and prognosis of the disease. To detect breast cancer early, there are therefore screening programs in the form of annual palpation examinations from the age of 30 and X-rays of the breast (mammography) from the age of 50, which are taken over by the statutory health insurance. A regular self-examination of the breast should be carried out once a month in the sense of early breast cancer detection.

If the diagnosis is confirmed breast cancer, therapy should be initiated immediately. The most important therapeutic pillar is the surgical removal of the tumor, which thanks to modern surgical techniques is nowadays possible in most cases while maintaining the breast. If, due to the size of the tumor, or because of your desire, the entire breast has to be removed, a reconstruction with implants or muscle tissue can be performed afterwards. Also in this method, the cosmetic results are very convincing nowadays.

Following the operation, in most cases, local irradiation will be carried out with the aim of destroying the residual tumor tissue. Depending on the nature and characteristics of breast cancer, further treatment options are available, each of which must be selected individually. In addition to classical chemotherapy, hormone therapies (endocrine therapies) and immunotherapies (antibody therapies) are often used successfully.

Definition and frequency

Breast cancer (breast cancer) is a malignant breast cancer. Breast cancer is the most common malignant tumor disease and the second most common cancer death cause (after lung cancer) in women. In Germany, between 65,000 and 75,000 women fall ill each year. Statistically, every eighth woman develops a breast cancer in the course of her life.

But even men can be affected by the disease. Although a much smaller proportion (about one in every 100 cases of breast cancer affects a man), these are usually highly malignant tumors that occur at an early age.

In women, the probability of breast cancer increases continuously from the age of 20, in order to reach between the age of 60 and 65, the peak frequency.

causes

The exact causes of the development of breast cancer have not yet been conclusively clarified. Recent studies assume that chance could play a far greater role than previously thought. This would explain why the majority of cancer cases arise spontaneously, that is without cause.

However, various risk factors as well as genetic predispositions that can promote the occurrence of breast cancer are known. In addition to advanced age and female gender, this includes a large breast (macromastia) and an initially benign multiplication of the glandular tissue (mastopathy). There are also hormonal and general risk factors that may be involved in the development of breast cancer.

Hormones can support cancer cells

The growth of the mammary gland is mediated by the action of certain hormones: Estrogens and progestogens are responsible not only for the initial development of the mammary gland during puberty, but also for the growth of the breast during pregnancy and during the menstrual cycle. The mammary gland tissue has specific receptors for this purpose, in which the hormones can bind and set a growth stimulus.

Unfortunately, estrogens and progestins can also promote the development and proliferation of some cancer cells via this route and are therefore considered risk factors for breast cancer. Hormonal risk factors are:

  • an early first menstrual period (menarche) and late onset of menopause (menopause). Especially in combination, these two factors create a long hormonally active period, which can have an adverse effect on the development of breast cancer.
  • no or few pregnancies and short breastfeeding
  • Overweight, especially in the postmenopause. Fat cells have an enzyme that enables them to produce estrogen.
  • Hormone replacement therapy (HET) in the postmenopausal period
  • long-term use of female sex hormones (eg the pill)

General risk factors

There was a clear correlation between the general risk factors and the development of breast cancer in numerous studies. Many of these factors are also crucial in the development of other cancers. General risk factors include:

  • Smoke
  • alcohol
  • Diabetes mellitus
  • radiation
  • certain malignant pre-existing conditions: ovarian, uterine or colorectal cancer in the patient's own history
  • Breast cancer of the other breast

The genes also play a role

For every fourth woman suffering from breast cancer, there are other breast cancer cases in the family, such as a sister or mother. This suggests that hereditary predisposition plays a major role in the onset of the disease.

To date, two genes have been identified that are causally linked to breast cancer: mutations in the BRCA-1 or BRCA-2 gene are inherited as an autosomal dominant gene and are associated with up to 80% risk in the course of life to contract a breast cancer. It is also typical that on average, BRCA-positive carcinomas develop 15-20 years earlier than those without familial risk. Changes in the BRCA gene continue to increase the risk of other types of cancer: In women, especially ovarian cancer (ovarian cancer); in men, there is also a greater chance of developing prostate or colon cancer.

To detect changes in the BRCA gene, a genetic test may be useful. This is usually offered or carried out if one of the following criteria applies:

  • Three or more women in the family suffer from breast cancer
  • Two or more women in the family suffer from breast cancer, of which at least one is ill before the age of 51
  • At least one woman in the family suffers from breast and at least one ovarian cancer
  • At least one woman in the family suffers from both breast and ovarian cancer
  • Two or more women have ovarian cancer
  • At least one woman within the family suffers from a bilateral breast cancer and is ill before the age of 50
  • At least one woman within the family has breast cancer before the age of 35
  • a male relative suffers from breast cancer and a female relative from breast or ovarian cancer.

Particularly relatives of the first degree, ie parents, children or siblings, are considered "related" or part of the family.

If an altered BRCA gene is detected, this is not accompanied by a special therapy that leads to a repair of the gene and thus reduces the risk of breast cancer - because such a therapy does not currently exist. However, women who belong to one of the above-mentioned risk groups are entitled to a half-yearly screening examination at the gynecologist from the age of 25 already. Furthermore, if there is a risk constellation, it is possible to have the breast tissue removed as a precaution and to rebuild the breasts with an implant in the same surgical procedure.

Read also:
Questions and answers about the risk of breast cancer

classification

The classification of breast cancer is based on the tissue of origin. Ductal carcinomas arise from the milk ducts, while lobular carcinomas arise from the mammary glands and are in principle located deeper in the breast. Both forms possess precursors, so-called precursor lesions, which can form long before the onset of carcinoma and are characterized by the absence of metastases. The precursor lesion of the ductal carcinoma is the ductal carcinoma in situ (DCIS), the precursor lesion the lobular carcinoma analogous to the LCIS (lobular carcinoma in situ).

Invasive ductal mummy carcinoma

With 70-80%, invasive ductal carcinoma is the most common form of breast cancer. It arises from the cells of the milk ducts and can therefore lie relatively close to the skin surface or even spread to the nipple or the surrounding skin. In such a case, the breast carcinoma is then called the Paget's disease of the nipple (Mamille). Characteristic of the invasive ductal form is that it occurs only in one place (unifocal growth) and develops comparatively quickly, within 10 years, out of the DCIS.

Invasive lobular carcinoma

Invasive lobular carcinoma is much rarer at 10-15% than invasive ductal. It arises from the glandular tissue. The invasive lobular form is often characterized by multicentric localization, which means that many foci can emerge within a breast at the same time. However, the incidence of bilateral lesions is also not uncommon in invasive lobular carcinoma at just under 40%. Left untreated, the LCIS can become a lobular carcinoma in about 25 years.

Gradient and special forms

Breast cancer does not always remain asymptomatic for a long time: in the case of Paget's disease of the mamilla as well as of the inflammatory breast carcinoma there are complaints that are atypical for a tumor disease.

Morbid Paget's disease

Mammal Paget's disease is usually caused by a DCIS or invasive ductal carcinoma of the milk ducts that spreads to the nipple and infiltrates the surrounding skin. Typically, this leads to a significant retraction of the nipple, which is red, scaly and itchy. In many cases, bloody secretions from the nipple come out. Paget's disease may resemble an inflammatory change in the nipple and should always be safely distinguished from this benign finding.

Inflammatory breast cancer

Inflammatory breast cancer is a very advanced stage (UICC stage IV) of an invasive carcinoma in which the tumor cells spread into the lymphatic channels of the skin. In most cases, the inflammatory carcinoma is based on a ductal carcinoma, in rare cases, a lobular. The infection of the lymphatic channels of the skin causes inflammation, which causes swelling, reddening and induration of the breast. Carcinoma does not respond well to therapy and is associated with a poor prognosis.

Localization: above all above

By creating a horizontal and a vertical line, which are at 90 ° to each other and whose point of intersection is on the nipple, the breast can be divided into four squares: In an upper outer, an upper inner and in a lower outer and a lower inner quadrant.

In most cases, breast cancer is located in the upper outer quadrant. That's because most of the glandular tissue is here. In 10-15% upper and lower outer as well as the nipple are affected, whereas in the lower inner quadrant only 5% of all carcinomas are affected. Furthermore, with every fourth carcinoma, a second occurs within a breast, so a thorough examination is essential.

When the tumor spreads: metastasis

For both forms of breast cancer, early metastasis via the blood and lymphatic channels is typical. The probability of tumor spreading in the body increases with its size.

Metastasis via the lymphatic system occurs in lymph nodes of the equatorial armpit and more rarely in the lymph nodes above and below the collarbone and the opposite breast. Breast cancer spreads breast cancer mainly in the bones, lungs and liver. Rarer, but also typical are dislocations in the brain, ovaries and spleen.

In the case of a positive lymph node finding of the armpit, an already spread of the tumor via the bloodstream is very likely.

Learn more about the classification here:
All important questions about the different types of breast cancer

symptoms

Unfortunately often only recognized late

The tricky thing about breast cancer or cancer in general is that it usually does not cause any symptoms such as redness, swelling or pain at the onset. Only in advanced stages do invasive carcinomas of the chest show clinical symptoms such as:

  • poorly defined, pressure-insensitive nodules or indurations in the chest that can not be explained by another disease
  • Skin retractions and persistent redness limited to one site of the breast
  • inflammatory altered and painful skin
  • Orange skin (thickening of the skin with point-like retractions, as normally occurs only at the buttocks)
  • Retractions of the nipple
  • Inflammation and discharge of the nipple (often bloody or purulent)
  • Size changes of the breast, which leads to an asymmetry of the breasts in the side comparison
  • different appearance of the two breasts in comparison when lifting the arms over the head
  • palpable and pressure-insensitive lymph nodes in the armpit
  • in very advanced stages, the tumor may spread or break through (exulceration)

These findings do not necessarily mean that there is breast cancer. However, if you feel a worrying finding in a breast or recognize any of the above symptoms, a timely medical examination is essential!

Later also general exhaustion and tiredness

In early stages, breast cancer is usually treatable well. However, if the disease progresses unnoticed, it can lead to other symptoms such as:

  • fatigue
  • in performance
  • fever
  • night sweats
  • weight loss
  • Pain

These symptoms can be an indication that the tumor has already formed settlements in the body and are generally associated with a worse prognosis.

Read also:
Important questions and answers about the symptoms

Diagnosis and differential diagnoses

Early diagnosis and treatment of breast cancer are critical to the disease process. For this reason, you should always see a doctor in a timely manner if you feel a knot or induration in your chest, or if you notice changes in your breasts as you look in the mirror.

At the first presentation, the gynecologist will ask for your medical history and important accompanying information in a detailed conversation (anamnesis). He then palpates both breasts and underarms and the clavicle regions exactly. If the tumor becomes suspicious, an ultrasound examination is performed in women under 40 years of age, and an x-ray examination of both breasts (mammography) in women over 40 years of age. Since these diagnostic methods are not feasible in every doctor's office, an appointment in a special center may be necessary.

X-ray examination (mammography)

Mammography is a good way to differentiate malignant from benign changes in breast tissue, to determine the size and number of lesions, and to estimate an approximate extent of the tumor. A decisive advantage of mammography is that precursor forms of breast cancer can already be detected. Microcalcifications that characteristically deposit in the ducts of the mammary gland tissue, as well as blurred limited space requirements with star-shaped foothills, are highly suspicious for a malignant tumor disease.

A disadvantage of the method is the radiation exposure. Mammography is performed if the tumor is suspected from the age of 40 and offers a high level of diagnostic certainty. In case of unclear findings, it can also be supplemented with an ultrasound examination.

More on this topic can be found here:
Important questions and answers about mammography

Ultrasound examination (sonography)

In general, the ultrasound examination is offered in women under 40 years and as a supplement to mammography (often in very dense mammary tissue). Sonography allows a good assessment of the breast tissue, but also of lymph nodes in the armpit and in the clavicle region.

A major disadvantage of ultrasound diagnostics is the lack of detection of precursor lesions of breast cancer that can already be visualized in mammography. An advantage is the absence of radiation, which justifies examinations even in very young patients.

biopsy

In order to finally be able to clarify whether a change in the breast tissue is benign or malignant, a tissue sample (biopsy) of the tumor must be taken. This is then examined by a pathologist under the microscope (histology) and assessed according to certain criteria of malignant or benign.

If malignant breast cancer is present, the pathologist may continue to determine what shape (ductal or lobular form) it is and how aggressive (rapidity of growth) the tumor is. In addition, it can be determined whether the tumor forms receptors that increase its growth under the influence of estrogens.

Staging tests

If it is suspected that mammary carcinoma, due to its aggressiveness or its advanced stage, has already formed metastases in other organs such as the lungs, brain or liver, so-called staging follows after the diagnosis is confirmed. This is made up of further studies to determine which organs are affected by the cancer and which treatment strategy is best. Classically, the staging of breast cancer includes:

  • an x-ray of the lung
  • an ultrasound scan of the liver
  • an investigation of the metabolic activity of the skeletal system
  • a CT scan of the ribcage or abdominal cavity

differential diagnoses

Changes in the breast or within the breast tissue must be differentiated from a whole range of other diseases. What many do not know is that even benign changes in the breast can lead to hardening and can be associated with nodule formation. To get a safe diagnosis and to start with the right therapy, a visit to the doctor is inevitable.

Among the benign changes that must be distinguished from a breast cancer include:

  • inflammatory changes of the breast such as abscess or mastitis
  • benign tumors such as the fibroadenoma, which results from an increase in glandular and connective tissue
  • Swelling that occurs during breast growth, often painful to the touch and classified as harmless
  • benign changes of fatty tissue or skin

Read also on this topic:
Questions about early detection and diagnostics

stadiums

The staging of breast cancer is based on the TNM classification, which is a widely used method for the systematic classification of malignant tumors. The TNM classification allows an estimation of the prognosis of the respective carcinoma and offers an important element in the selection of the appropriate therapy.

T (= tumor) stands for the extent and behavior of the tumor itself, N (= Nodus) for the involvement of regional (near the tumor) lymph nodes and M (= metastatic) for the presence of tumor-distant metastases (distant metastases). The numbers following the letters give information on the size of the tumor as well as on the pattern of involvement of the lymph nodes.

TNM classification of breast cancer

Tis Carcinoma in situ (LCIS or DCIS)
T1 Tumor size: <2cm
- T1a: ≤ 0.5cm
- T1b:> 0.5cm and ≤ 1cm
- T1c:> 1cm and ≤ 2cm
T2 Tumor size:> 2cm and ≤ 5cm
T3 Tumor size:> 5cm
T4 Tumor of any size with simultaneous involvement of the skin or the chest wall; also an inflammatory breast cancer is automatically assigned to the stage T4.
N1 Infestation of 1-3 lymph nodes in the axillary region or along the sternum on the affected side. The lymph nodes are mobile.
N2 Infestation of 4-9 lymph nodes that are not motile, but fused with tissue in the region:
- N2a: The lymph nodes are located in the axillary region.
- N2b: The lymph nodes are located next to the sternum, on the side of the affected breast. The armpits are free.
N3 Infestation of more than 10 lymph nodes that are not displaced and:
- N3a: below the collarbone,
- N3b: both in the armpit and next to the breastbone,
- N3c: located above the collarbone.
M1 There are distant metastases. Distant metastases are all metastases located outside the breast or adjacent lymph node regions, for example in the lung, liver and skeletal system.

 

For example, a tumor that measures 3 cm in size, has two lymph nodes, and has no distant metastases is thus assigned to T2N1M0.

UICC classification of tumor stages

The UICC classification summarizes the different manifestations or combination possibilities of the TNM classification and helps with therapeutic decision-making. Depending on how large the tumor is, how many lymph nodes are affected and if there are distant metastases, it can be decided which therapeutic approach should be followed, which therapy methods are used and if a cure is sought (curative approach) or a life extension or an improvement in the quality of life through the therapy (palliative approach).

Stage 0 Tis
Stage I includes the TNM stages:
T1a N0 M0
T1b N0 M0
T1c N0 M0
Stage IIA includes the TNM stages:
T0 N1 M0
T1 N1 M0
T2 N0 M0
Stage IIB includes the TNM stages:
T2 N1 M0
T3 N0 M0
Stage IIIA includes the TNM stages:
T0 N2 M0
T1 N2 M0
T2 N2 M0
T3 N1 M0
Stage IIIB includes the TNM stages:
T4 N0 M0
T4 N1 M0
T4 N2 M0
Stage IIIC every T N3 M0
Stage IV
every T every N M1

 

More on this topic can be found here:
Worth knowing about the spreading diagnostics

Important for the therapy: the receptor status

In addition to the assignment of breast cancer to the respective UICC stage, the determination of the receptor status is of crucial importance. This is not included in the UICC classification, but is essential for choosing the right therapy.

There are three differences: hormone receptor-positive, HER2 / neu-receptor-positive and tripelnegative status.

Hormone receptor-positive breast cancers produce hormone receptors that can be stimulated by endogenous hormones such as estrogen or progesterone to increase in size under the influence of hormones. HER2 / neu-positive tumors receive growth stimuli from the body's own messenger substances, which are usually responsible for the natural growth of the body. In HER2 / neu-positive breast cancer, the influence of HER2 / neu leads to a faster division of the tumor cells and thus to the growth of the cancer.

Tripelnegative tumors have neither estrogen, progesterone nor HER2 / neu receptors. What may seem positive at first sight is a major challenge in the treatment of breast cancer, because while a specific receptor therapy can be followed by a specific therapy, triple-negative cancer therapy is much less undirected and therefore often less effective ,

treatment

The treatment of breast cancer distinguishes between surgery, radiation and drug-based tumor therapy. These forms of therapy are used in both curative and palliative approaches.A curative therapy is used when the treatment is supposed to cure the disease. A palliative approach is followed when the cancer is in a state where it can not be cured by conventional therapy. It is then by the treatment but quite an extension of life or a reduction of the symptoms possible.

The therapy of breast cancer is very individual, a selection of therapeutic measures is carried out among others according to the following criteria:

  • UICC stage
  • receptor status
  • Older
  • treatment goal

1. Locally limited stadiums (I & IIA)

Locally limited tumor stages are characterized by a tumor size of less than 2 cm, with an infestation of a maximum of three regional lymph nodes. Remote metastases do not occur. The claim to therapy is complete healing without loss of life or quality of life, which is often achieved with a good overall prognosis (5-year survival of 90%).

Operation as a means of choice

The core of curative therapy in the stages I & IIA is the surgery, which aims to remove the tumor without leaving the breast. As a rule, a breast-conserving therapy (BET) is sought, in which only the tumor tissue is removed, while the remaining breast or glandular tissue stops. Indications for a BET are:

  • a favorable relation of tumor size and breast volume
  • only one tumor focus

If a BET is not possible or not desired by the patient, a radical mastectomy is performed. In this case, the entire breast is removed and then optionally rebuilt with an implant. A plastic reconstruction of the breast can be performed either at the same time as tumor removal or at a later time.

Indications for a complete removal of the breast are:

  • multiple tumor centers within a breast
  • incomplete removal of the tumor after previous BET
  • presumably unsatisfactory cosmetic result of BET
  • a re-irradiation is not possible

Various studies have shown that BET and radical mastectomy do not differ in their long-term outcome.

Sometimes the lymph nodes have to get out too

An important aspect of the surgical removal of the tumor is to determine to what extent lymph nodes are already affected. In this case, the lymph node is identified, which first receives the lymph fluid coming from the breast and passes it on. This lymph node is called the sentinel lymph node and is removed and evaluated during the operation.

The standard for an assessment of the sentinel lymph node is the histological examination, which is usually carried out in the frozen section procedure during the operation time by a pathologist. If this investigation reveals that the sentinel lymph node is not affected, removal of the lymph nodes in the armpit and subsequent irradiation of the same can be dispensed with. The same applies if no more than two lymph nodes are affected and the tumor does not exceed T2. However, if 1-3 lymph nodes have metastases, they must either be completely removed or included in the subsequent irradiation of the tumor bed.

Read also:
Important questions and answers about breast surgery

Irradiation after surgery

Following a breast-conserving therapy, a local irradiation is usually performed. This can be shown to reduce the risk of recurrence of the tumor (tumor recurrence). Irradiation includes both the tumor area and the adjacent chest wall, with a higher dose of radiation normally being used for the immediate area of ​​the tumor (boost) than for adjacent areas. There are two schemes available for irradiation:

  • The conventional method consists of 25 sessions spread over 5 weeks. Each session is irradiated with 25 Gy.
  • The hypofractionated method is performed over 3 weeks (15-16 sessions) with 40-42.5 Gy per session.

Various studies have shown that the results for recurrence risk, survival and cosmetic outcome are comparable for both methods. Side effects such as edema, breast shrinkage, redness and vascular changes are less frequent in the hypofractionated method.

After a complete mastectomy in tumor stage I or IIA, irradiation of the tumor area or the adjacent chest wall is generally not necessary.

If radiotherapy and chemotherapy are not recommended following surgical removal of the tumor, radiation should be initiated 4-6 weeks after surgery. If both chemotherapy and radiation are scheduled, treatment is usually combined, starting with chemotherapy and later with radiotherapy. Irradiation should be started no later than half a year after surgery.

More about this topic can be found here:
Worth knowing about radiotherapy

To weigh exactly: chemo

Depending on the hormone receptor status of breast cancer, chemotherapy (adjuvant chemotherapy) may be necessary following surgery and in addition to radiation. This demonstrably reduces the risk of recurrence and significantly reduces the cancer-specific mortality rate. The decision for or against chemotherapy is very individual and is always a case by case decision. Orientational criteria are used that speak for or against chemotherapy and serve as a basis for decision-making.

Adjuvant chemotherapy is usually recommended if:

  • more than four lymph nodes are affected,
  • the tumor divides rapidly (high Ki-67 index),
  • the tumor cells are very aggressive and strongly altered (G3),
  • the tumor has already attacked vessels,
  • there is a positive hormone receptor status,
  • the tumor is HER2 / neu negative.

Adjuvant chemotherapy significantly reduces the risk of breast cancer recurrence. However, individual benefit depends on many factors and can not be predicted. In addition to the biological characteristics of the tumor (such as the hormone receptor status), the tumor stage, concomitant diseases and the selection of the chemotherapeutic have effects on the response of the therapy and the success of therapy.

Individually tailored therapy

If the decision is made for therapy, two to three chemotherapeutic agents are selected, which are either combined and administered simultaneously or sequentially. Also for the combination or the gift of chemotherapy there is currently no gold standard. As with the decision for or against chemotherapy, the choice of medication must be made individually.

Standard schemes for localized or non-metastatic breast cancer are:

  • the FAC scheme from the three preparations: 5-FU, adriamycin and cyclophosphamide
  • the FEC scheme from the three preparations: 5-FU, epirubicin and cyclophosphamide

Alternatively, 5-FU can be replaced by chemotherapeutics from the taxane group.

Since chemotherapeutic drugs attack cells that divide quickly, particularly fast regenerating organs are affected by the side effects of the drugs. Nausea and vomiting, hair loss, inflammations of the mucous membranes, changes in the blood picture with increased tendency to bleed and susceptibility to infection are common. In addition, generalized fatigue and general fatigue are characteristic side effects of chemotherapy.

More information here:
Questions and answers about chemotherapy

Starve the tumor: anti-hormone therapy (endocrine therapy)

Hormone receptor-positive breast carcinoma (a carcinoma that produces progesterone or estrogen receptors and grows under the action of these hormones) may be used to endocrine therapy alternatively or in combination with chemotherapy. The basis of this method is the drug blockade of the estrogen and progesterone receptors or the inhibition of the formation of these hormones, which deprives the mammary carcinoma of the basis for growth and can lead to a reduction in the size of the tumor.

75-80% of all women with breast cancer have a positive hormone receptor status, which is why a tailored to the hormone receptor status chemotherapy is the rule rather than the exception in the treatment of breast cancer. There are three drug groups available that differ in their mode of action:

  • Antiestrogens (Tamoxifen: Tamokadin®, Kessa®, Mandofen®, Nolvadex®, Toremifen: Fareston®) block the action of estrogens directly on the tumor cells. The most widespread in Germany is tamoxifen.
  • GnRH analogues (Enantone®, Trenantone®, Zoladex®) block the formation of estrogens in the ovaries by reducing the secretion of LH and FSH in the diencephalon. Since this process only takes place before menopause, GnRH analogues are used exclusively pre-menopausal.
  • Aromatase inhibitors (anastrozole: Arimidex®, letrozole: Femara®, exmestane: Aromasin®) inhibit an endogenous enzyme responsible for the production of effective estrogens from its precursors. By inhibiting the enzyme (especially in adipose tissue), no active hormone forms can be formed, which leads to a growth inhibition of the tumor.

Tamoxifen before the menopause

The choice of medication depends on the endocrine therapy after menopausal status. Women who are not yet menopausal are treated with tamoxifen. Tamoxifen blocks the estrogen receptors of tumor cells and thus inhibits the estrogen-dependent growth of mammary carcinoma and its metastases.

However, the reduced estrogen levels are not without danger: Tamoxifen can cause a number of side effects such as nausea, flushing, rash, fluid retention, calf cramps, drowsiness, bone pain and thrombosis. Since tamoxifen has a growth-promoting effect on the tissue of the uterus, the risk of developing uterine cancer increases over time.For this reason, the drug should not be used for more than five years.

Before the menopause, combining tamoxifen with GnRH analogs may be useful. As these reduce the formation of estrogen in the ovaries, they have an additive effect on tamoxifen. If antihormonal therapy is performed following chemotherapy, the combination of tamoxifen and GnRH analogues is no more effective than tamoxifen alone, and therefore GnRH analogues are not used in this situation.

After menopause first aromatase inhibitor

Women who have already passed menopause will be treated differently: initial therapy will be provided with aromatase inhibitors such as letrozole, anastrozole and exmestane for a period of two to five years, followed by tamoxifen for another five years.

The side effects of aromatase inhibitors are similar to those of tamoxifen. In addition to hot flashes, sleep disorders and weight changes may also cause muscle and joint pain and a reduction in bone density (osteoporosis). Serious side effects, which fortunately rarely occur, are an increased tendency to thrombosis as well as strokes and malignant uterine tumors. As the ovaries largely cease functioning during menopause, therapy with GnRH analogs no longer makes sense.

Targeted against the tumor

In addition to the estrogen or progesterone receptor status, breast cancer is always examined for another receptor, the HER2 / neu receptor. A positive finding, which is the case in about 15-20% of breast cancers, is both a curse and a blessing, because HER2 / neu-positive breast cancers are generally associated with a worse prognosis; however, for some years, a specific therapy exists that can only be used with this feature of the tumor: Trastuzumab (Herceptin®) is an artificially engineered antibody that binds to the HER2 / neu receptor on the surface of cancer cells and thereby inhibits tumor growth. Trastuzumab is infused once a week for at least one year and is comparatively well tolerated.

Read also:
Important questions about hormone therapy

2. Locally advanced stages (IIB, IIIA, IIIB, inflammatory breast cancer)

Even in locally advanced stages is the therapy claim the cure, that is the cure. However, the risk of recurrence at these stages is significantly higher and above all dependent on the spread of the tumor in the diagnosis, the lymph node involvement as well as the biology (hormone receptor status) of the tumor. Despite the worse initial situation, the 5-year survival rate is 70-85%.

Hormone and chemotherapy before or after surgery

Therapy in the locally advanced stages IIB and III is very individual and always a case by case decision. In the presence of a positive estrogen and progesterone receptor status as well as in the detection of HER2 / neu is generally advised to a drug chemotherapy. This can be done either before or after surgery and radiation.

Chemotherapy before surgery offers several advantages. Firstly, the tumor's response to chemotherapy can be directly observed, and secondly, the rate of breast-conserving therapies increases. Advanced chemotherapy may continue to be combined with anti-HER2 / neu therapy for positive hormone receptor status and then completed by endocrine therapy. While the antibody against HER2 / neu can be given directly with taxane-based chemotherapy, endocrine therapy with anti-estrogens, GnRH analogs or aromatase inhibitors is given following chemo and before surgery.

However, drug endocrine therapy may also be performed following surgery and radiation. In the case of positive hormone receptor status, antiestrogens, GnRH analogues and aromatase inhibitors are administered analogously to the locally limited stage.

Various studies have shown that overall disease-free survival is equally good in both cases. The decision as to whether hormone or chemotherapy should be carried out before or after surgery and radiation is therefore dependent on the general condition and the tumor-specific treatment planning and always individually.

Surgery and subsequent irradiation

As in the locally limited stage, breast augmentation (BET) is also aimed at the surgery of locally advanced breast cancer, which is completed by a subsequent irradiation. If BET is not possible or not desired, radical mastectomy may be performed, removing all of the breast tissue. Standard in both cases is the removal of the labeled sentinel lymph node. If this occurs, all lymph nodes of the axillary region are removed (axillary dissection) and this region is also irradiated following the operation.

Depending on the location of the breast carcinoma, irradiation from other adjacent lymph node regions may also be useful.
Axillary dissection and axillary region irradiation should always be carefully considered as these actions may be associated with an increased risk of lymphatic drainage disorders and may severely limit quality of life.

3. distant metastasis (stage IV)

Distant metastases, ie, breast cancer in other tissues, occur despite early diagnosis and advanced therapy in about 20% of cases.In this situation, no curative treatment can be done, the therapy is then usually palliative. This means that the aim is no longer to heal, but to have as few residual symptoms as possible. The use of medication at this stage of the disease helps to alleviate physical and mental discomfort and, in many cases, life extension.

Like the other stages of breast cancer, stage IV is treated very individually. The following factors are considered prognostically favorable:

  • Good general condition
  • Metastastes exclusively in the skin, skeleton and lymph nodes
  • a positive hormone receptor status
  • the recurrence-free interval was more than two years
  • no pretreatment of a metastatic stage

4. Special forms

Infestation of a single organ

If distant metastases are found only in a single organ or in a single location (for example in the liver, lungs, sternum or brain), the combination of local therapy (irradiation or surgical removal of the metastasis) with drug therapy can provide an above-average Annual survival can be achieved. As a rule, the medical treatment of the local treatment is progressing.

Hormone receptor positive breast cancer

A distant metastatic hormone receptor positive breast cancer is mainly treated with endocrine therapy, which can achieve very good recovery rates of up to 30%.

The treatment of choice in premenopause is the reduction of the body's own estrogen formation via the elimination of the ovaries. In most cases, this is achieved medically by GnRH analogues, but in a few cases also by surgical removal of the ovaries.

Another important therapy pill is tamoxifen, which reduces the effect of estrogen on the tumor tissue and thus deprives it of its growth basis. Alternatively, endocrine pretreatment or side effects may be treated with the estrogen receptor blocker fulvestrant (Falslodex®), which is usually combined with a CDK4 / 6 inhibitor Palbocicilb (Imbrance®).

In the postmenopause, GnRH analogs are not used, but aromatase inhibitors that inhibit the formation of estrogens in adipose tissue. Alternatives are also tamoxifen and fulvestrant. Here, the choice of drugs depends crucially on which drugs were administered in the primary therapy, when the distant metastases occurred and which medications have been best tolerated so far.

A postmenopausal therapy with positive hormone receptor status can be expanded to include substances that specifically inhibit signaling pathways on the tumor cells and thus can reduce the growth of tumors and metastases. Possible candidates for this purpose are the mTOR inhibitor everolism (Certican®) and the CDK4 / 6 inhibitor palbocicilb.

The endocrine therapy is usually continued until the cancer continues to grow despite therapy (Progress). However, the side effects of the treatment must always be weighed against the continuation of the therapy.

HER2 / neu-positive breast cancer

In recent years, the treatment of metastatic HER2 / neu-positive breast cancer has been expanded to include new, effective drugs. As in the context of curative therapeutic approaches, the antibody trastuzumab is accorded great importance. The antibody binds to the HER2 / neu receptor on the tumor cells and thus prevents growth. Under trastuzumab up to 20% remission rates could be achieved, which could be increased by up to 50% by combining the antibody with various chemotherapeutic agents such as antracyclines, taxanes or platinum derivatives.

A new substance that acts like trastuzumab but binds to another domain of the HER2 / neu receptor is pertuzumab (Perjeta®). The combination of this anti-HER2 / neu antibody with trastuzumab and a taxane was able to achieve remission rates of 80% in studies.

Triple-negative breast cancer

If there is no positive hormone receptor status or HER2 / neu receptor, breast cancer is called triple-negative. The triple-negative breast cancer is extremely heterogeneous, which is also reflected in the localization of its distant metastases, which are often found in atypical regions. Both the primary therapy and the treatment of metastases are very individual and depends on specific parameters. To be considered in this context:

  • the growth rate of the tumor
  • the type of metastasis
  • the biology of the disease

A gold standard of treatment does not exist due to the different manifestations of the carcinoma.

Relieve weight: symptomatic therapy

While the three therapeutic approaches for the treatment of metastatic breast cancer have always pursued the causative approach to stem tumor growth, symptomatic therapy aims to reduce physical and mental discomfort without affecting tumor growth. The symptomatic therapy is therefore a very important part of the overall palliative concept and should always be initiated early and comprehensively.

The most important approaches of symptomatic therapy include the treatment of:

  • bone metastases
  • brain metastases

Bone metastases can lead to great pain in the musculoskeletal system and to an irregular fracture tendency. The treatment of choice is the irradiation of the metastases, which leads to a strengthening of the bone structure and alleviates pain.Furthermore, depending on the number of metastases and fragility of the skeleton, medical and surgical intervention is possible.

Brain metastases can lead to inflammatory swelling of the brain with subsequent symptoms of pain and failure. The drug of choice for relieving the symptoms is the administration of glucocorticoids. For a single metastasis, surgery may be useful. Whole brain irradiation, which is also a common therapeutic measure, must always be weighed well, as it may improve local tumor control but may also lead to memory impairment.

complications

Both the disease itself and the treatment of breast cancer can lead to complications requiring further therapeutic intervention. The most important are:

  • the accumulation of bloody fluid between the lungs and the chest wall (pleural effusion), which, depending on its severity, is manifested by shortness of breath and chest tightness and can only be treated by a puncture
  • a shift in the electrolyte balance due to a massive release of calcium (hypercalcemia) from the bone in the presence of distant metastases in the skeletal system
  • Fractures with only slight strain (pathological fractures) due to the instability of the bone structure
  • Lymphedema of the arm after removal and irradiation of the axillary region (axillary dissection)
  • Development of uterine cancer as a result of tamoxifen therapy

forecast

The prognosis of breast cancer depends on how early the tumor was detected and treated. Other factors that are prognostically important are:

  • the axillary lymph node status as the most important prognostic factor. This is understood as the involvement of the lymph nodes of the armpit. The prognosis worsens with increasing number of affected lymph nodes.
  • the size of the primary tumor according to TNM classification
  • the presence of a positive HER2 / neu receptor status as a negative prognostic factor
  • the absence of hormone receptor status (unfavorable factor)
  • the growth rate as well as the differentiation of the tissue. A fast growth and a poor differentiation worsen the prognosis considerably.

More about this topic can be found here:
Around prognosis and course

prevention

Provision is worthwhile!

Preventive measures help to detect breast cancer at an early, mostly treatable stage.
The statutory health insurance takes over once a year a breast examination by the gynecologist in women from the age of 30 years. Every two years, women over the age of 50 are entitled to a mammography screening every two years until the age of 69, which in favorable cases can detect breast cancer before it is palpable.

The likelihood of developing breast cancer once in life is further reduced by the following parameters:

  • an early first pregnancy
  • several births before the age of 30
  • long breastfeeding
  • regular exercise

Read also:
Important questions and answers about precaution

 

Author: Lisa Wunsch

sources

B. Wöhrmann et al .: DGHO German Society for Hematology and Medical Oncology, https://www.onkopedia.com/en/onkopedia/guidelines/mammakarzinom-der-frau/@@view/html/index.html, last accessed 05/10/2017.

German Cancer Society (DKG) and German Cancer Aid, Interdisciplinary S-3 Guideline for the Diagnosis, Therapy and Aftercare of Breast Cancer, http://www.awmf.org/uploads/tx_szleitlinien/032-045OL_k_S3__Brustkrebs_Mammakarzinom_Diagnostik_Therapie_Nachsorge_2012-07.pdf, last accessed 10.05. 2017th

U. Fischer, F. Baum: Diagnosis and Therapy of Breast Cancer, Thieme Verlag, 2014.

K. Goerke et. al .: Clinical Guide Gynecology and Obstetrics, Urban & Fischer, 2013.

J. Marjoribanks et al .: Long term hormone therapy for perimenopausal and postmenopausal women, Cochrane Database of Systematic Reviews, 2012.

 

Comment: The most important questions and answers about breast cancer

Breast cancer is certainly among the most dreaded diagnoses. Breast cancer, the technical term, is the most common cancer in women in the Western world. No other female cancer claims more deaths. Every eighth German is at some point affected by it in the course of her life. Around half of the women are under the age of 65 at the time of diagnosis, around one in ten people under the age of 45. A shock when you or woman (every 100th breast cancer patient is a man) is confronted with it. So good news ahead: many women do not die from their breast cancer. Especially if the diagnosis is made early in the course of the disease.

Do not panic: you have time!

The next important info: You have time! In any case, more time than you would like to believe in the first, fearful moment. Breast cancer is usually not an emergency. The perceived time pressure after diagnosis puts a strain on many women. But he is usually "homemade". Driven by one's own fears, possibly reinforced by well-intentioned recommendations from the medical and private sectors, to go immediately to inpatient treatment.

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No question - if there is a suspicion of breast cancer in the room, there is much to do and set the right course.But take the necessary time to digest the first shock and get enough information and an overview. Then you have ground again under your feet and have a clear mind and the necessary knowledge about better decision-making. Our compilation of important questions and answers, which is constantly being expanded, should help you with this. Because the cure for breast cancer and the subsequent quality of life depend not on the fastest possible, but on the best possible treatment and care.

No surgery without biopsy - and if possible not without MRI

Incidentally, the diagnosis of breast cancer can not be confirmed by palpation or imaging (X-ray, ultrasound, MRI). This is only possible in conjunction with the removal of suspicious tissue (biopsy), which is then examined histologically in the laboratory. It is about the question of whether the changes are benign or actually malignant. Fortunately, in the majority of cases, sensed lumps in the breast are benign and not breast cancer. The MRI examination, also known as the "core spin", also provides slightly false-positive results when considered alone, ie findings that appear like a breast cancer but are not. However, on MRI tissue changes and their extent can be detected better than with X-rays or ultrasound. So if the diagnosis is breast cancer, you should insist on an MRI before surgery. This can be used to avoid stressful and sometimes momentous re-operations. In addition, if necessary, further, previously unrecognized tumors can be located elsewhere in the breast.

Although experts and the so-called S3 guideline recommend the MRI examination for surgical planning as the highest technical guideline, the statutory health insurance funds continue to refuse to pay for it. However, there are breast centers that offer this procedure regardless of their insured status. It is also important to be able to clarify the histological findings only in MRI. This requires an MR-controlled vacuum biopsy.

Your right: a tailor-made treatment - and a second opinion

In addition to general, psychological and everyday practical questions, in advance of breast cancer treatment, there are also more or less detailed medical questions on diagnostics and therapy. It can not hurt to deepen oneself more deeply into matter. But it is also understandable if this seems too tedious and too complicated for you. In any case, before starting the treatment, have your doctor tell you in detail what he suggests based on the available findings. In doing so, express your own fears, wishes and needs for tailor-made treatment and follow-up care.

Claim your right to a second medical opinion, paid by the health insurance. So you do not show a lack of confidence in your doctor. On the contrary: the more you are convinced of the necessity and meaningfulness of the measures to be carried out, the better it will be for everyone involved - but above all for you and your chances of success. Because from a medical point of view, the first treatment after the diagnosis is important. And in all likelihood you will be demanded enormous energy and energy resources. A walk looks different.

Optimum care in certified breast center

An optimal care is the basis for a successful companion on the way to healing. In the majority of cases, the medical procedure consists of surgery and follow-up treatment with radiation, hormone therapy or chemotherapy, either alone or in combination. Depending on the individual situation, neoadjuvant chemotherapy may be useful before surgery. From a qualitative point of view, you are best placed in a certified breast center. There, the specialization and the high treatment volume ensure great experience and the best possible standards. Highly qualified and currently trained staff works interdisciplinarily, ie beyond medical specialist boundaries. It may be worth it to take a bigger path and not to go to the next best facility around the corner. Your resident (women's) doctor should be involved in the care process right from the start and then take care of the aftercare in your familiar surroundings as much as possible.

Looking ahead - and to the here and now

The medical treatment and care is one side. The other, at least as important aspect is your self-management. Dejection, sadness and fears for the future are quite normal in such a situation. Especially after the diagnosis and after the provisional completion of the intensive treatment phase, when the energy reserves are used up. Give yourself time, be friendly and patient with yourself. But stay active or become it. Take advantage of the unexpected life plan change to do something for your physical, mental and emotional resilience. Sport improves the chances of recovery, mental fitness too.A healthy diet and social contacts are important and beneficial. Consider taking a confidant with you to the doctor's talks. In order to deal with one's own fears, it can also be very helpful to speak to an uninvolved person, such as a psycho-oncologist. Take advantage of the experiences of other stakeholders, be it via the Internet and its forums or in direct contact, such as in a self-help group. But keep in mind that no two cases are alike. Unfortunately, in such forums sometimes exaggerated horror scenarios spread, and so general that they almost never apply to you, but spread a lot of fear.

It is important to look forward, but above all to the here and now. For some cancer patients, this knowledge is one of the most valuable experiences in dealing with the suffering.

Author: Dr. Hubertus Glaser