Mammary cancer

Causes of late cancer detection

Most women complain on presence of a compaction in the gland, which is usually painless and often accidentally detected. If a woman undergoes preventive mammography, the cancer is detected before clinical manifestations, when the neoplasm is still small. But even a large-sized cancer node in a large breast may not show symptoms. With a sufficiently large size of the neoplasm, there might be a discomfort in the armpit and its tumidity.

Cancer emerges in the epithelium of the gland ducts, but by the time of diagnosis, it has already grown in most women from the duct into the lobules, spreading inside the gland and radially, after which the tumor involves the chest wall with ribs.

Mammary gland symptoms

The formation in the mammary gland is very dense, it may be lumpy, with a fuzzy demarcation from normal tissues, skin growing to it, sometimes the skin above the node is drawn in like a navel. Tumor cells overlap the small lymphatic ducts, the skin becomes pimply like lemon, that is why it was named «lemon peel». The tumor pulls tight the tissue inside the gland and locks the nipple.

Symptoms of some mammary cancer varieties

Usually the tumor has a nodular form, when the boundaries of the cancer are fuzzy but identifiable. If the tumor spreads throughout the mammary gland without forming a node, but infiltrating all the tissues causing their swelling and inflammation, such form is called inflammatory.

This aggressive variety of the condition has severe symptoms, like any inflammation, but this is not true inflammation due to the presence of microflora, but an acute tissue reaction to the penetration of cancer cells into it. Such a course of the malignant process is accompanied by an increase in breast size, a sharp pain and burning redness of the skin. Very early, tumor cells invade lymph nodes and cause their painful enlargement.
When a neoplasm grows in a large excretory duct, there may be peculiar symptoms of discharge from the nipple, it is possible that the secretion is stained with blood which is called «bloody», secernating or «weeping» gland. Symptoms may incluse pain localized within the organ.

Symptoms of metastases

There is a variety of the disease when the tumor destroys the chest, but does not generate distant metastases, only to the nearest lymph nodes. Why this happens is unknown. Yet in most cases, metastases first emerge in the axillary, and then in the subclavian and supraclavicular lymph nodes. At the same time, the tumor is spread with blood, which is accelerated and aggravated by damage to the lymphatic network and the spread of cancer cells through it. It is metastases that lead to death.

In some cases, manifestations of metastases become the cause of seeking medical assistance, more often in the bones, having the form of permanent pain not subsiding at rest, and mobility limitation due to pain. Symptoms of the skeletal lesion are not always obvious, as most metastases do not manifest themselves either in pain or a violation of the bone integrity. As a rule, clinical manifestations are present on the side of the pelvic, hip and lumbar vertebrae which experience a large load.

When cancer cells penetrate into the bone marrow, blood composition is disrupted: the population of cells of all three lineages is reduced, bruises easily appear and nose bleeds occur, and the body’s resistance to infections is drastically reduced.

Metastases to the lungs and pleura are manifested by coughing and shortness of breath, and formation of pathological fluid called pleurisy. Liver damage is manifested by symptoms of digestive disorders with changes in appetite, nausea, frequent vomiting, weakness, jaundice, and an increase in abdominal volume due to ascites.

Clinical symptoms of mammary cancer may be minor or severe, the Clinic Medicine 24/7 will always find a way to reduce the pathological manifestations of the condition applying chemotherapy and special rehabilitation methods. The patient in any state will be offered several promising options of palliative treatment. Sign up for a consultation: +7 (495) 151-14-47

Mammary cancer types

Mammary cancer, also called carcinoma, is the most common oncological condition.

At all stages starting with 1, the choice of medication approach is determined by the biological type of the tumor.

With hormonal dependence (luminal type A), a long-term antihormonal therapy is prescribed.

With positive estrogen receptors and high aggressiveness (luminal type B), hormones are combined with chemotherapy. When the drug resistance marker HER2 is detected, chemotherapy is combined with a drug that neutralizes resistance.

The non-luminal type is characterized by the absence of hormonal dependence in drug resistance (the type with overexpression of HER2), and chemotherapy is performed with taxanes and anthracyclines.

If there are no receptors and HER2 in the tumor (triple negative or basal-like type), chemotherapeutic treatment is performed.

Mammary cancer symptoms

The appearance of clinical signs of a malignant process in the mammary gland is not an evidence of early breast cancer, which can be cured in the vast majority of 90–95%. In an ideal case, the condition is found during a routine examination, when it still does not manifest itself, is not detected by palpation and is visible only with a mammography or MRI.

Palpation is performed in supine position. Breast is probed in circular motions from the edge to the center, not forgetting the armpit area and lymph nodes.

A malignant neoplasm in the gland does not hurt, unless it globally disrupts the circulation of blood and lymph. Pain can be felt in the tissues surrounding a large cancer node, which are compressed by a rapidly growing conglomerate, and in metastases in the axillary lymph nodes located near neurovascular bundles. Skin ulcers are almost painless, more worrying is the unpleasant smell and plentiful discharge, even the disintegrating nodes in the glandular tissue are only a little painful. Pain is not the main and not the first symptom of mammary cancer, and the cancer node does not hurt for most of its life.

Oncologists recommend women to perform regular self-examination for detection of tumor nodes. The examination is best performed on the 5-7th day of the cycle, since breast tissue density changes under the effect of sex hormones.

Examination includes visual inspection and palpation. Palpation is performed in supine position. Breast is probed in circular motions from the edge to the center, not forgetting the armpit area and lymph nodes.
All symptoms of breast cancer can be divided into 3 groups: cutaneous, changing the gland structure and associated with the nipple.

Speaking of cutaneous symptoms, any local long-term existing change in the skin of the gland should be alarming, such as:

• Non-smoothing wrinkles in a limited area or «lemon peel» skin, under which a formation can be determined;
• Compaction of a skin area or its painless swelling;
• A funnel-like retraction resembling navel, with an underlying compaction of glandular tissue;
• A long-lasting painless ulcer with a dense rim;
• A painful reddening and a significant increase in the size of one breast due to puffiness, often with a pronounced venous pattern.

Structural changes:

• A local and uneven deformity of the gland;
• Loss of symmetry, an enlargement or on the contrary, a diminishing of some department;
• Compaction of glandular tissue without clear boundaries.

Nipple symptoms:

• Locked nipple immobility, often with an asymmetric deformation;
• Discharge of blood or clear fluid does not always imply a malignant process, however, it is a symptom of some trouble in the milk ducts;
• A non-healing ulcer of the nipple or its areola, any changes in its skin;
• Pronounced differences and dissimilarity with the nipple of the other breast.

Mammary cancer diagnostics

Mammary cancer diagnostics is a preparatory stage for treatment, until its termination it is impossible to decide on an individual treatment plan, or even say whether there will be an operation. The treatment tactics is determined by the size of the tumor node and the process advancement outside the organ, not counting other cellular markers.

Mammography for early diagnostics of mammary cancer

Mammography is included in the three required examinations, although today it has been replaced by MRI of the mammary glands devoid of significant deficiencies. Mammography is also performed at preventive examination, since it is a quick, inexpensive and informative method to survey the entire breast tissue and identify nodes not detectable by palpation. A bilateral examination is always performed, given that every 20th patient may develop cancer in both glands, not necessarily at the same time.

A major drawback of diagnostics is that in women of childbearing age the glandular tissue is poorly visible after 5–10 days after the onset of menstruation due to fluctuations in its density under the effect of hormones. At all other times, the tumor merges with the background of the mammary gland, so young women are subjected to an ultrasound scan to determine the cancer location, the number and size of the axillary lymph nodes.

Breast MRI ensures even more precise identification of the tumor and metastases in the lymph nodes.

Mammary cancer biopsy

Each condition has its own «datasheet specifications» manifested in a characteristic tissue structure. Cancer diagnostics is based on identifying the cellular composition of the tumor before any therapeutic manipulations. In the last century, surgery was sometimes performed without morphological confirmation of cancer, first performing a sectoral resection, and then a mastectomy after cancer identification. This approach was rejected because it promoted spreading of tumor cells outside the gland due to blood affluxion during the operation.

The simplest option of morphological diagnostics is mammary tumor puncture, but it is not always possible to get the result at the first try due to the increased formation density. Moreover, cytological diagnostics by studying the cell under the microscope gives only a presumptive diagnosis. The accurate diagnosis and accordingly the correct direction in the choice of treatment are ensured only by morphological diagnostics after core biopsy, when a tissue column is taken for a histological examination with a special needle. The manipulation does not spread cancer cells, entails low trauma and allows full study of tumor tissue composition.

The final diagnosis is established only by histological examination of the entire removed mammary gland. The tumor will be cut into many thinnest layers and preserved, enabling its study for several decades.

Diagnostics of distant metastases

Examination is performed on areas of probable and most frequent metastatic spreading: chest, abdominal and gynecological organs, and skeleton bones. The state of the organs nearest to the affected gland is assessed by digital chest radiography. It should be borne in mind that while X-ray imaging shows formations more than a centimeter, CT can detect smaller metastatic lesions. Changes in the abdominal cavity and small pelvis will be revealed by ultrasound, but CT and MRI scans will be more accurate.

Osteoscintigraphy, or bone scanning, is performed out with complaints of pain or movement disorders. Isotopes introduced into the vein will settle in areas of any pathological changes, and their concentration will vary in intensity of luminescence, given that metastatic foci accumulate more contrast material.

Immunohistochemical study (IHC)

The tumor of each woman is mandatorily examined for presence of sex hormone receptors. If cancer cells contain such receptors, hormone therapy is prescribed. Estrogen (ER) and progesterone (PR) receptors are determined, but only the first are of clinical importance, while progesterone receptors are used to determine the sensitivity of estrogen to therapeutic exposure. A very good result of hormone therapy is expected when both receptors have a high concentration.

When planning treatment, it is necessary to determine the resistance of cancer cells to chemotherapy, which is shown by the level of HER2 expression. If the analysis fails to finally determine the presence of HER2 by an immunohistochemical method, then a more complex test is performed using the FISH or CISH hybridization method.

Current diagnostic standards include determining the Ki67 proliferative activity index, which shows the aggressiveness of the tumor. The indicator is expressed as percentage, but so far there is no unanimity in the choice of treatment based on Ki67.

Oncomarkers

Of course, in certain cases the question arises about the possibility of genetic cancer inheritance. By now we have come to understand that sporadic and hereditary breast cancer are different diseases, and accordingly the therapeutic approaches are not the same. Genetic testing is needed for cancer development up to 35 years and existence of cancer patients in family history. If a woman has previously suffered ovarian or colonic cancer, then BRCA1 and BRCA2 mutations are also likely.

Errors of breast oncologists contributing to reduction of the patients’ life:

The erroneous orientation of the patient to preserving the breast without taking into account the condition stage and without the objective prerequisites to do so. The contribution of this factor is approximately 10% in the total mortality from mammary cancer.

A false negative diagnosis, when a comprehensive initial examination was completed and a preliminary diagnosis was established, but the biopsy was falsely performed on a healthy zone and/or the histological study had an inadequate quality. This tragic mistake contributes 2–5% to the total mortality.

Erroneous underestimation of the surgery scope, when instead of the subcutaneous mastectomy, a sectoral resection is performed, or instead of the radical mastectomy, any other surgical intervention is performed.
False negative postoperative biopsy, when a histological and/or immunohistochemical study of the material removed from a woman erroneously does not reveal cancerous cells at the resection margins. As a result, there is a relapse and a repeated resection, contributing 2–5% to the total mortality

An inadequately selected chemotherapy, given that the ideal basis for any complex immune, hormonal, and polychemotherapy is ensured by comprehensive genetic testing based on both the definition of point mutations specific to mammary cancer and the determination of the entire tumor genotype. It is accountable for about 50% of premature deaths

A short polychemotherapy, most often it happens that 2–4 cycles are performed instead of 3 sets of 7 cycles required by the NCCN recommendation, for a total of 21 cycles. This factor gives about 30% of all cases of premature death from mammary cancer.

Mammary cancer treatment methods

Surgical mammary cancer therapy

Only surgery guarantees women a cure for cancer. Clinical studies have convincingly proved that, according to the forecast, a partial removal of breast tissue with subsequent irradiation is not worse compared to complete breast removal, that is, resection and mastectomy are equivalent in terms of the result expressed as life expectancy without any tumor signs. Surgical approach depends on the tumor size and the degree of its aggressiveness. With a neoplasm, beginning at stage 0 and even at stage 3 of an initially operable process, an organ-preserving surgery is possible, of course, if the volume of the mammary gland itself allows. The larger is the reproductive organ, the greater is the surgical capability to preserve it.

Organ-preserving operative interventions include sectoral or segmental resection, also known as lumpectomy or quadrantectomy, when the tumor and at least 3 centimeters of surrounding healthy tissue are excised. Healthiness is crucially important, as there should be no cancer cells at the margins, which is checked by an urgent histological examination in the course of surgery. If at least one cancer cell is found under a microscope on the edges of the removed tissue, the surgeon will perform an additional excision called «re-resection», and send the tissue for histology. Radiation therapy is always performed after resection and wound healing and, if necessary, after several cycles of chemotherapy.

Mastectomy means complete removal of the gland together with adipose tissue from under the scapula and armpit, various modifications also entail removal of some pectoral muscles. Current standards also regard as absolutely radical the subcutaneous mastectomy, when all of the above is removed in a single block leaving a skin «pouch» for implant installation. A subcutaneous or skin-preserving surgery is possible only in the absence of cancer cells in the skin. The implant can be installed at once or after a while, and the process of artificial breast recreation is called reparative surgery. After completing special treatment, some women are offered corrective surgery on a healthy gland for symmetry.

With metastases to the axillary lymph nodes, they are completely removed along with cellular tissue (lymphadenectomy) in addition to a radical resection or mastectomy. The presence of metastases is detected during surgery with a biopsy of the sentinel lymph node, the one closest to the breast.

Chemotherapy

After surgery, chemotherapy is not performed with a cancer nodule less than 5 millimeters in the absence of metastases in the lymphatic basin ascertained by histological study, because additional medication will not change a woman’s life for the better.

In all other clinical situations, the issue of additional drug exposure is necessarily resolved after surgery. Preventive chemotherapy should preclude relapse and metastases, or postpone their appearance for as long as possible.

Chemotherapy treatment is necessarily based on the molecular biological subtype of the malignant tumor. It is possible to refrain from preventive chemotherapy with a high hormone dependence of the cancer, and a long-term hormone therapy is prescribed instead in such cases.

With an initially inoperable cancer, antitumor treatment starts with chemotherapy, prior to which a piece of tumor is taken for study of its cellular structure. The effect of the use of cytostatic drugs before surgery is expected in the absence of signs of hormonal dependence in the tumor, its high aggressiveness, and a triple negative type of cancer. Schemes with the most active cytostatics are applied, and treatment takes about six months, even with a significant decrease in the tumor after initial cycles. The benefits of treatment are undoubted if it was possible to completely or maximally reduce the cancer node, creating the technical conditions to performing radical surgery.

At stage 4 of mammary cancer, drug therapy is the leading method of treatment that begins with chemotherapy, then, in the presence of hormone receptors in tumor cells, perennial hormone therapy is performed. In very elderly women with a number of serious conditions and signs of hormonal sensitivity, hormonal drugs are applied at the first stage.

Hormone therapy

Given the unconditional dependence of cancer on the activity of the endocrine glands, it is far from always that the tumor responds to hormonal drugs. The efficacy of therapeutic hormones is predicted by the level of sex hormone receptors, estrogens and progestins. In principle, a positive result is possible with one percent of estrogen-dependent tumor cells, but the higher is their level, the greater is the benefit.

Hormone therapy is performed after the operation or instead of it in case of a metastatic condition. Currently, hormonal drugs are used even at cancer stage 0, the goal being not to prevent the appearance of metastases, but to prevent cancer development in another gland.

Preventive or adjuvant hormone treatment at any stage takes at least 5 years, if metastases occur during this time, then chemotherapy is performed and the hormonal drug is changed. With a metastatic process, hormonal agents are applied before progression.

Choice of the hormonal drug depends on the state of the menstrual function, accordingly only Tamoxifen is prescribed to menstruating women, while aromatase inhibitors and Tamoxifen are prescribed after menopause (the last menstruation in life).

Clinical studies did not help to choose the best endocrine drug, as both groups of drugs showed high efficacy and similar complications, but with different frequency of occurrence.

Radiation mammary cancer therapy

At the present stage, radiation therapy is a high-tech method that requires a CT scan and an X-ray simulator for optimal calculation of irradiation fields, this is 3D treatment on electron or proton accelerators.

The goal of irradiation is to kill all cancer cells and preserve the viability of normal tissues adjoining the tumor. The task of radiation therapy for mammary cancer is to prevent a relapse in the surgery area, therefore, at any stage irradiation complements radical resection.

At stage 2–3, irradiation is also performed after mastectomy, in some cases it is intensified by a ‘boost’ that makes it possible to bring more radiation power to the local area of the cicatrix. Radiation therapy begins after wound healing, that is, not earlier than 4 weeks after surgery.

If the patient requires chemotherapy, the necessary number of cycles is first performed, and irradiation is started after a couple of weeks in order to avoid severe radiation reactions. The period for radiation therapy commencement after surgery is quite broad, ranging from one to three months.

With an inoperable process, radiation therapy also starts 2–4 weeks after a full course of chemotherapy and can be performed together with hormone therapy. To improve the effect, it can be supplemented by local hyperthermia.

Radiation therapy always starts on Monday and ends on Friday leaving the weekend free, which allows normal tissues to recover. The number of sessions is determined by the goal — preventive treatment takes at least 25 days, while curative therapy of a non-removed tumor requires 30–35 procedures.

Radiation therapy does not affect life expectancy, but protects the woman from cancer recurrence.

Life expectancy at different stages of mammary cancer

The stage of cancer is important for choosing the optimal treatment tactics, and oncologists have noticed a definite connection between life duration and the cancer node size at the time of its detection.

• At stage 1, the probability of survival is many times greater than the possibility of death from cancer, 90% will be cured and will forget about their illness.
• At mammary cancer stage 2, more than half of the patients will live at least 5 years, and can live for a very long time and die of a cardiovascular disease at an extremely old age.
• At stage 3, only every third patient will live for 5 years or more.
• At mammary cancer stage 4, active chemotherapy and hormonal exposure would allow to live for 2 years or even more.

However, all these calculations are very tentative, as no one knows how the tumor would behave and what factors can reliably predict the patient’s fate. There are numerous cases when after removal of a large tumor with metastases in the lymph nodes women live for 20 and 30 years, and at stage 1, rapid generalization occurs. Prediction of the condition course relies on the degree of cancer cells aggressiveness and their sensitivity to drugs, but this was not enough to ensure accuracy. Currently, there is no system or formula that allows predicting the patient’s fate, the main thing is that every woman should be given adequate and most comfortable cancer treatment that does not interfere with her further living. The Clinic Medicine 24/7 offer such treatment today.

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Sergeev Petr Sergeevich

Head of oncology department, oncologist, surgeon, candidate of medical science

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Questions most frequently asked after diagnosis

Why did it happen so?

Hereditary predisposition is one of the key factors in the development of mammary cancer. In total, more than 10 different marker genes have been studied. Determination of mutations of the BRCA1 and BRCA2 genes has become commercially widespread. In women with mutations of these genes, the risk of developing an oncological condition ranges from 50 to 85%.

Could I have caused the condition myself?

All commonly mentioned factors associated with development of mammary cancer, including consumption of alcohol or red meat more than 5 times a week, low content of dietary fiber and natural antioxidants in food, potentiate the natural predisposition. The total impact of these and other environmental factors, including breast injury, radiation therapy on the chest area, and others, does not exceed 10–20%.

Did I miss some symptoms?

Even in quite prosperous countries of Northern Europe that have a public system of early diagnostics, more than 30% of all new cases are found BETWEEN regular mammographic examinations, these are the so-called «interval cancers» of the breast. Classical signs of the condition that include a nipple shape change (retraction) and solid immobile formations with uneven edges in the gland itself, may remain invisible in the presence of a fibrocystic mastopathy, in women with large breasts, after plastic surgery. Currently, patients are becoming more common at the stage of locally advanced cancer with enlargement of lymph nodes in the armpit, with the effect of «orange peel» over the node.

Is it possible to avoid surgery?

In principle, in case of breast cancer irrespective of the primary diagnostics stage, due to the specific features of the oncological process any given surgery from organ-preserving resection up to subcutaneous mastectomy with simultaneous implant installation will be performed during the patient’s life. Therefore, it is wrong to decline surgery, or even worse, to be afraid of it! An early resection and 15 years of life are better than palliative mastectomy and 6 months of life. The choice is yours, and you need to be afraid not of surgery, but of the illness!

Is minor surgery possible?

The scope of resection is determined by the tumor process stage. The most modern method of determining the stage is a biopsy of the sentinel lymph node with subsequent histological study. If no tumor cells are detected in the sentinel lymph node, then the risk of lesion of other lymph nodes is minimal and they are not removed. In this case, the scope of surgery is limited to the glandular tissue of the mammary gland, without crippling removal of the pectoral muscles and transection of outflow paths of the lymph from the arm that leads to chronic lymphostasis or even gangrene.

See a photo report from the operating room. A surgery for mammary cancer with simultaneous impant installation

The material was prepared by the oncologist and gynecologist, surgeon of the Clinic Medicine 24/7 Ivan Igorevich Bokin, Candidate of Medical Science.

Reference list:

1. Bazhenova A.P., Ostrovtsev L.D., Khananashvili G. N. Mammary cancer (In Russian) // Moscow, Medicine Publ., 1985, 272 pp.
2. Chissov v. I., Daryalova S. L. Oncology (In Russian) // Мoscow, GEOTAR Media Publ., 2007.
3. Bulynskiy D. N., Vasilyev Yu. S. Modern methods for diagnosis and treatment of mammary cancer (In Russian) // Chelyabinsk, Chelyabinsk State Medical Academy, 2009, 84 pp.
4. Mammology. A national manual (In Russian). v. P. Kharchenko, N. I. Rozhkova (Eds.) // Moscow, GEOTAR-Media Publ., 2009, 328 pp.