In situ breast cancer on mammography. Treatment of ductal carcinoma in situ of the breast (DCIS) and its effectiveness

Oncology mammary gland can be called a fairly common disease. Cancer begins to develop epithelial tissue mammary gland.

The situation when malignant cells do not affect other tissues and organs, but grow inside the mammary glands, is called non-invasive cancer, or in situ.

Non-invasive breast cancer has a fairly favorable prognosis and is a treatable cancer.

Causes and symptoms

This kind oncological disease develops due to many factors.

Doctors consider the most important of them:

• hereditary predisposition;
• taking medications containing hormones;
• the presence of fibroadenoma or fibrocystic mastopathy;
• taking oral contraceptives;
• individual characteristics of the reproductive system.

Risk factors for this disease include any hormonal imbalance female body, childlessness or large families, late first births or even late onset of menopause.

It can also be provoked by smoking and alcohol, gynecological diseases, atherosclerosis, liver disease, excess weight, hypertension and frequent stress. The risk of cancer also increases with age, that is, in women under 40 it is 0.5%, and in women from 40 to 60 years old it is already as much as 4%.

It is not possible to talk much about the symptoms of in situ breast cancer, since in most cases there are no symptoms at this stage. They appear only later, if the disease begins to move into an invasive form.

But sometimes this disease also has its own symptoms, namely:

• pain in the chest;
• redness of the gland;
• discharge from the nipples;
• edema.

If at least one of these signs occurs, you should immediately go to the doctor and undergo an examination. It should be remembered that although stage zero breast cancer is not considered deadly, it can still lead to invasive cancer.

Forms of non-invasive breast cancer

Stage zero breast cancer is divided into ductal and lobular carcinomas. They differ from each other in the location of the tumor.

As mentioned above, non-invasive cancer is located only in certain areas of the breast and does not affect other organs.

In no case should one not take this disease seriously and postpone its treatment, since both ductal and lobular carcinoma can become invasive and begin to move to neighboring areas of the breast and even to other organs.

This is the most serious complication of non-invasive cancer. In most cases, ductal carcinoma passes into the invasive stage after 5-7 years, and lobular - after 15 years.

Prevention and diagnostic measures for the detection of non-invasive breast cancer

The initial stage of breast cancer is very difficult to diagnose and has almost no pronounced symptoms.

In most cases, the presence of ductal or lobular carcinomas can be established on mammography. This type of examination is mandatory for suspected breast cancer and other diseases of the mammary glands.

The next stage of the examination is such a study as a biopsy. To detect in situ breast cancer, minimally invasive types of this medical procedure are used, namely fine-needle aspiration and core-needle biopsy.

In fine-needle analysis, a tonne needle is inserted deep into the suspicious area of ​​\u200b\u200bthe gland and a tissue sample is taken with a syringe. This procedure does not leave behind any scars.

A core biopsy proceeds in the same way, only a thicker needle is selected, and a larger tissue sample is also obtained. Most often, before inserting the needle, a small incision is made in the skin, which facilitates the procedure. After it, a small scar remains, which after a while becomes invisible.

The tissue samples extracted as a result of this procedure are examined under a microscope and tested for the presence of hormone receptors.

In order to reduce the risk of this disease, you need to take care of your health, especially hormonal background. The birth of the first child under the age of 30 and breastfeeding significantly reduces the risk of developing oncology. Also, a woman should be serious about choosing hormonal contraceptives.

plays an important role in the prevention of carcinoma healthy lifestyle life. Of course, it is very important to have regular check-ups with a specialist. This is especially true for women over 35. And women over 45 need a mammogram every year. Younger girls can do this less often, but only if they are not at risk.

Treatment for Stage Zero Breast Cancer

The most proven and successful treatment for non-invasive cancer is surgery. Most often, doctors use a mastectomy. But, in addition to breast removal, sometimes organ-preserving treatment is also chosen.

Only after examining the patient's history, and after conducting all the necessary tests, the doctor can decide how to properly treat the patient.

But there are groups of people for whom only a mastectomy is suitable. These include:

Stage zero breast cancer can be treated with breast-conserving procedures such as lumpectomy and quadrantectomy.

1. A lumpectomy is an operation to remove the area of ​​the breast with a tumor, as well as a small amount of healthy tissue surrounding it. Such a surgical procedure can be prescribed only for patients with a tumor less than 4 cm.
2. A quadrantectomy is a surgical intervention in which part of the gland is removed from the nipple to the very edge, while affecting the fiber and The lymph nodes.

If a mastectomy is used, in which the entire mammary gland is removed, then the woman may have surgery to reconstruct the gland. It can be carried out both together with a mastectomy, and a year after this procedure.

Contraindications to any surgical intervention are:

• metabolic disorders in the body;
• extensive expression of the epidermis;
• circulatory disorders in the brain;
• severe cardiovascular failure.

After any surgical intervention The patient is given radiation therapy. It helps reduce the risk of recurrence of the disease. Also, in some cases, before the operation, the patient is offered to undergo a course of chemotherapy. It helps to make an inoperable tumor operable, as well as shrink the tumor and help preserve the mammary gland.

If the tumor is hormonally dependent, then hormonal therapy using antiestrogens can be used to get rid of it. This treatment is especially effective in elderly patients and with a minimum number of metastases.

Lobular carcinoma, which develops rather slowly, in most cases does not require surgical treatment. Sometimes doctors prescribe such medications like Tamoxifen, Anastrozole, Exemestane or Raloxifene. Taking these medications greatly reduces the chance of an invasive form of breast cancer.

Non-invasive breast cancer, although not fatal, is a rather serious disease that requires competent treatment.

If you are attentive to your health, this will help to identify this disease as early as possible and eliminate it even before it has time to cause any harm to the body. After curing the zero stage of cancer, you should also visit the doctor regularly.

The term "in situ" refers to the earliest stages of the malignant process, when a group of abnormal cells is located where it originated and does not spread to other areas. On microscopic examination, cancer cells are visible, but there is no germination of the tumor in other tissues.

Causes

It is still impossible to say exactly why pathology occurs. It is believed that changes in individual genes (mutations) cause dysfunction of cells. Sometimes mutations occur naturally when DNA is replicated during cell division. There are factors environment, which can damage DNA and increase the chance of cancer in situ:

• substances found in tobacco smoke
• ionizing radiation
• ultra-violet rays.

There are also chemicals that are considered carcinogens that provoke the development of tumors. It is not necessary that cancer will occur after contact with the substance, it depends on the time of exposure and the individual characteristics of the person. Consider dangerous, for example:

• arsenic
• asbestos
• benzene
• benzidine
• beryllium
• coal tar and soot
• crystalline silica
• ethylene oxide
• formaldehyde.

What's happening?

If cancer in situ occurs in squamous cells, the condition is called carcinoma in situ (CIS) or intraepithelial cancer. In some guidelines, this pathology is considered a zero stage of cancer.

Scientists identify several features of this process:

• Cancer in situ has no vessels. Perhaps this is what limits the growth of education.
• Abnormal cells appear at the same rate as they die, i.e. the size of the tumor does not increase.
• The lesion affects certain types of cells, for example, the transitional epithelium of the urinary tract, the epithelium of the mammary glands, stratified squamous epithelium vaginal part of the cervix.

ICD codes

The disease is classified under headings D00-D09 - "in situ neoplasms". Depending on the localization, the following carcinomas that have arisen in situ are distinguished:

• oral cavity, esophagus and stomach - D00
• other and unspecified digestive organs - D01
• middle ear and respiratory organs - D02
• leather - D04
• mammary gland - D05. Subdivisions: lobular carcinoma in situ - D05.0, intraductal carcinoma in situ - D05.1, other carcinoma in situ of the breast - D05.7, carcinoma of the breast, unspecified - D05.9
• cervix - D06
• genitals - D07
• other and unspecified sites D09, including carcinoma in situ, site unspecified D09.9
• melanoma - D03. Pathology has many subsections in situ: melanoma of the lip - D03.0, eyelid - D03.1, ear and external auditory canal - D03.2, other and unspecified parts of the face - D03.3, scalp and neck - D03.4, trunk - D03.5, upper limb - D03.6, lower limb- D03.7, other localizations - D03.8, unspecified localization - D03.9.

Symptoms and signs

The tumor is not visible to the naked eye. Due to its small size, it does not manifest itself in any way, and the patient does not feel any changes in his condition.

In situ cancer diagnostics

The condition can only be "caught" by examining tissue under a microscope. Sometimes, for a complete diagnosis, sections of a tissue sample are studied in different projections. This allows you to make sure that there is no germination of the tumor.

Usually, the diagnosis of pathology at this stage occurs by chance, for example, during an examination by a gynecologist.

Treatment

Usually, organ-preserving surgical methods are used. As a rule, the affected area of ​​the epithelium is removed with a small amount of healthy tissue around. For example, for cancer in situ in the cervical region, several treatment options are possible: cryodestruction, laser or electrosurgical removal, scalpel removal.

If the affected area is large or there are several foci with altered cells, then a more extensive surgical intervention is performed. Thus, in ductal carcinoma of the breast with multiple in situ cancer sites, a mastectomy is performed, i.e. removal of the mammary gland.

Is cancer in situ dangerous?

Since this is the very beginning of the tumor process, there is no great danger. The five-year survival of patients is 100%. However, without treatment, the process with big share likely to progress to the first or more advanced stages of cancer.

Prevention

There are proven ways to reduce the likelihood of developing cancer. To do this, eat enough fruits and vegetables (at least two servings a day), reduce exposure to direct sunlight, try not to smoke, increase physical activity, and avoid the potential harmful effects of carcinogenic chemicals.

Thanks to the development of mammography techniques and the introduction of mammographic screening, the frequency of detecting clinically latent forms of both minimal breast cancer (BC) and carcinomas in situ (CIS) has significantly increased. According to the world literature, CIS currently accounts for 20-40% of all newly diagnosed cases of breast cancer.

In 1908, Cornil described the similarity of invasive cancer cells with cells limited to the epithelium of the ducts, and Cheatle and Cutler were among the first to suggest that carcinoma in situ is a form of cancer, initially represented by a pool of malignant cells, limited to the epithelium, not involving the basement membrane, but potentially invasive. The term CIS of the breast combines two types of disease with different biology, risk of developing invasive cancer and methods of treatment: ductal carcinoma in situ (ductal carcinoma in situ-DCIS) and lobular carcinoma in situ (lobular carcinoma in situ-LCIS). The most commonly diagnosed is DCIS.

Morphologically, DCIS is a relatively heterogeneous disease. Most of its classifications are based on the morphological structure of the tumor, which allows us to distinguish two main types of DCIS - comedo and non-comedo DCIS. Such a division, on the one hand, is associated with the diametrically opposite prognostic significance of these types of DCIS, and, on the other hand, is determined by the similarity of some morphological markers of non-comedo forms of DCIS. The latter are represented by cribrous, papillary, micropapillary, solid and “clinging” forms of ductal carcinoma.

This classification, although convenient for clinicians, as it clearly distinguishes prognostically favorable (non-comedo) and unfavorable (comedo) forms of DCIS, is extremely simplified, since it does not fully reflect the biological features of the growth of intraductal carcinomas in situ and does not take into account borderline forms of DCIS.

In order to overcome the shortcomings of traditional histological classification, many alternative classifications have been proposed in the last decade, based on factors such as the above-mentioned grade of malignancy (based on nuclear grade I, II, III) and the presence of comedonecrosis. Using a combination of these factors, Lagios, Silverstein et al. suggested that DCIS be classified into three histological grades: high grade (ICHM), intermediate grade (PSHM), and low grade (NSHM).

Most effective method The treatment of carcinoma in situ is still surgery. Mastectomy leads to almost 100% cure for the disease. At the moment, there are no convincing large randomized clinical trials comparing the effectiveness of mastectomy and organ-sparing surgery, however, the former remains the “standard” against which other methods of treatment are compared. However, in the last two decades, the majority of patients, even with invasive carcinoma, have undergone organ-preserving (conservative) treatment for certain indications, so the routine use of mastectomy in patients with DCIS is currently debatable.

Disputes regarding the extent of surgical intervention in DCIS continue, since so far, despite the emergence of a number of classifications, it is difficult to foresee which treatment will be the best in a particular case. However, there is a category of patients with DCIS (approximately 25%) who have an absolute indication for mastectomy:

1. patients with a large tumor size (more than 5 cm), which does not allow radical organ-preserving surgery;
2. patients with multiple foci of DCIS with a relatively small size of the breast;
3. patients who cannot undergo radiotherapy(for example, due to comorbidity or previous radiation therapy to the chest for another disease).

organ-preserving treatment. The initial result of the widespread use of salvage surgery (with or without radiotherapy) in DCIS was a significant increase in the incidence of local recurrence. The recurrence rate increased from 1-2% after mastectomy to 30-50% after organ-sparing treatment. The data obtained led researchers to look for risk factors that affect the frequency of relapses.

In multivariate analysis, Fisher et al. (1999) identified statistically significant features: histological grade, tumor size, and resection margin width. Silverstein, reviewing DCIS treatment data, noted significant differences in rates of local recurrence depending on the degree of histological malignancy. The frequency of relapses within 84 months. The follow-up rates for ASHD, PSGD, and NSGD were 41%, 16%, and 0%, respectively. According to Lagios et al. an increase in tumor size from 15 mm to 40 mm is accompanied by a doubling of the number of recurrences (25.5% and 57%, respectively), and an increase in the width of resection margins from 1 mm to 10 mm, on the contrary, leads to a decrease in the frequency of local recurrence by almost 5 times (from 42% up to 8.3%). Silverstein argues that with a sufficient resection width (10 mm or more), tumor size and histological malignancy have little effect on the rate of local recurrence.

Most recurrences occur either in the resection area or in its immediate vicinity, which indicates the inadequacy of surgical intervention (insufficiently wide excision of the tumor). However, to achieve adequate surgical resection of the mammary gland, it is very difficult to accurately determine both the true extent of the tumor along the ducts and the required resection width. R. Holland, using morphological studies, showed that in situ ductal carcinomas are almost always unicentric in genesis (i.e., involve only one duct in the process), but often multifocal (since multiple foci of the tortuous duct fall into a microscopic section in one segment mammary gland). Therefore, lesions are often larger than expected and tend to extend beyond the boundaries of mammographically detectable microcalcifications. In particular, R. Holland (1984) noted that in 40% of cases, the microscopic and radiographic dimensions of DCIS differ by more than 2 cm. The inaccurate orientation of the surgeon to the X-ray mammographic findings partly explains the high frequency of local recurrence during super-economical operations. The remnants of intraductal carcinoma in situ are the main source of relapses, and in the case of microinvasion, regional metastases.

In order to avoid recurrence and to perform a timely “saving” resection or even mastectomy, it is necessary to focus on a thorough morphological study of the margins of surgical resection, since “clean” surgical margins are one of the main criteria for organ-preserving treatment of DCIS. In addition, the X-ray method for examining the surgical material has found widespread use, which serves to immediately resolve the issue of expanding the scope of the operation in case of detection of microcalcifications in the surgical material along the resection margin (with subsequent urgent morphological confirmation of the presence of tumor remnants). For the same purpose, post-excision mammography is often performed.

In 90% of cases, the histological structure of the recurrent node is identical to the structure of the primary ductal carcinoma in situ. However, in some cases, recurrences occur far from the primary focus (although sometimes within the same quadrant), which indicates the development of the tumor de novo, and not from the remnants of previous DCIS, which can partly be explained by the multifocal nature of ductal carcinoma in situ. As a result, the expansion of the resection volume does not always prevent the development of local recurrences. However, true DCIS has characteristics that make radical tumor resection theoretically possible:

1. no stromal invasion;
2. unicentric distribution (in one ductal system);
3. absence of distant and regional metastases.

Thus, factors such as grade, presence of comedonecrosis, tumor size, and resection margin width are important predictors of the risk of local recurrence in patients undergoing organ-sparing treatment for DCIS. Silverstein and Lagios, using these signs in combination, tried to identify risk groups for the development of local recurrences. As a result, the researchers proposed Van Nuys Prognostic Index (VNPI). The basis of the VNPI is a 3-point gradation of each of the above signs: 1 - the best forecast, 3 - the worst. The prognostic index is equal to the sum of the scores obtained by assessing the size of the tumor, the width of the resection margins and the morphological study of the tumor. According to this gradation, in each individual case, from 3 to 9 points can be obtained. At 3-4 points, the frequency of local recurrence is low (I), at 5-7 - moderate (II), and at 8-9 points - high (III). The study found that the recurrence-free survival rates in each of these groups were statistically significantly different from each other.

In addition, to resolve the issue of the possibility of organ-preserving operations, the following conditions can be taken into account:

1. DCIS size should not exceed 2-3 cm in diameter; if the size of the tumor is estimated by microcalcifications on the mammogram, then its area should not exceed 6 cm2; with a greater spread of the tumor, an organ-preserving operation is possible only with a sufficient size of the mammary gland, which makes it possible to avoid significant deformation in the event of removal of a large amount of tissue;
2. the width of the resection edges should be at least 10 mm;
3. histological grade should be low to intermediate, although some investigators believe that patients with high histologically graded DCIS may also be candidates for organ-sparing surgery if there is a margin of 10 mm or more;
4. the mammary gland should look aesthetically pleasing after the operation; if this is not possible, it is preferable to perform a mastectomy (followed by breast reconstruction).

Axillary lymphadenectomy. Axillary lymphadenectomy in patients with DCIS is usually not performed, since the number of occult invasive carcinomas, accompanied by metastasis to the axillary lymph nodes, does not exceed 1-3%. Patients undergoing mastectomy have recently undergone a sentinel node biopsy. To identify these nodes, radioisotope probes are used to detect the accumulation of radiopharmaceuticals injected near the tumor (along with blue dye to visualize their exact location).

Radiation therapy (RT). The results of studies evaluating the effectiveness of postoperative radiotherapy in patients with DCIS, obtained at the present time, are very controversial.

The NSABP (B-17 protocol) was the first prospective study of the role of LT in organ-sparing treatment in patients with in situ ductal carcinoma. 818 patients underwent either only organ-preserving operations or organ-preserving operations followed by radiation therapy. As a result, a significant reduction in the incidence of local recurrences, especially relapses with an invasive component, was recorded among patients undergoing postoperative radiotherapy. The 3-year recurrence rate in patients with DCIS after organ-sparing surgery and radiation therapy was 10%, and after organ-sparing surgery without radiation therapy it was 21%. The 8-year recurrence rate was 12% and 27%, respectively, and after 10 years, 13% and 31%, respectively. The data obtained allowed the NSABP to recommend postoperative radiotherapy for all patients with ductal carcinoma in situ who are scheduled for salvage surgery.

However, for approximately 30-40% of patients with ductal carcinoma in situ undergoing organ-sparing surgery, subsequent RT, like mastectomy, is overtreatment. Therefore, in a number of studies, emphasis is placed on the careful selection of patients in whom the likelihood of an additional positive effect of RT is high.

Lagios et al. in his study tried to evaluate the effectiveness of RT in DCIS, taking into account risk factors for the development of local recurrences. Featured high efficiency RT for high histological grade DCIS, but no benefit of RT for low histological malignancy was found. In addition, it was noted that the risk of recurrence in DCIS with high histological malignancy increases in proportion to the increase in tumor volume, however, RT has practically no effect on recurrence-free survival rates, except in cases where the tumor size does not exceed 15 mm.

In the work of Lagios, the analysis of the effect of the width of the surgical margins on recurrence-free survival did not show statistically significant differences in groups with and without postoperative RT. The rate of local recurrences with a surgical margin of 10 mm or more was 4.5% without RT and 5% in the RT group. RT had a positive effect only in the group of patients with high histologically malignant DCIS with a margin width of 10 mm and 1-9 mm (recurrence rate of 0% and 29%, respectively, versus 8.3% and 40.5% without RT). With margins less than 1 mm wide, RT had no advantage over conventional tumor resection. In DCIS of low and intermediate histological malignancy, RT did not have a positive effect, regardless of the width of the surgical margins.

The use of the Van Nae prognostic index served as the basis for the development of a treatment algorithm, incl. radiation therapy of ductal carcinoma in situ. The results of treatment of three risk groups for the development of local relapses were analyzed. In the group with a low risk of recurrence (3-4 points), RT did not have a statistically significant effect. In the group with a moderate risk of recurrence (5-7 points), during RT, a decrease in the frequency of local relapses by 13% was noted. The greatest advantage of RT was registered in the group with a high risk of recurrence (8-9 points). However, in the latter case, the incidence of local recurrence was extremely high, regardless of whether RT was performed or not.

Based on the results obtained, recommendations for the treatment of DCIS were made. With a total index of 8-9 points, given the high risk of developing local recurrences (more than 60% in 5 years), it is recommended to perform a mastectomy. With an index of 5-7 points, a wide resection with postoperative RT is necessary, and with an index of 3-4 points, a sectoral resection of the mammary gland is sufficient.

Thus, indications for postoperative RT should be based on careful identification of risk factors for local recurrence of the disease.

adjuvant drug therapy. Adjuvant cytotoxic therapy is not available in patients with DCIS. Otherwise, the situation is with hormonal treatment. Randomized clinical trials conducted by B. Fisher in the NSABP project showed that the appointment of tamoxifen at a dose of 20 mg / day. within 5 years in patients with DCIS who underwent organ-preserving treatment and RT, reduces the frequency of invasive recurrences in the same mammary gland. In addition, hormonal therapy significantly reduces the incidence of both invasive and non-invasive recurrences in the contralateral breast. Tamoxifen improves recurrence-free survival regardless of the condition of resection margins and the presence of comedo-type necrosis. However, the administration of the drug does not affect the overall survival rates.

Whether tamoxifen should be used routinely in all patients with DCIS or used only in receptor-positive tumors is not yet clear. At the moment, there are no sufficient data with a statistically significant effect of tamoxifen treatment. The effectiveness of selective estrogen receptor modulators in the treatment of DCIS (raloxifene) is currently being investigated.

Treatment of patients with relapses after organ-preserving treatment. In invasive recurrence, treatment is consistent with that of invasive breast cancer of the same stage. Treatment for non-invasive recurrence depends on the initial treatment. If the patient has undergone only local excision, then re-excision, re-excision and RT or mastectomy are the methods of choice. In some patients, repeated attempts at local excision of the tumor can be made. If radiation therapy was performed, then when a relapse occurs, as a rule, a mastectomy is performed.

observation. All patients treated for DCIS require lifelong follow-up. Mammography is performed in all patients who have undergone organ-preserving treatment annually, and for the first two years after treatment, mammography should be performed every 6 months. Clinical examination of patients during the first years should also be performed every 6 months. and then annually. Other additional methods diagnostics have relative readings.

Conclusion.

1. DCIS is a relatively common disease. Thanks to mammography, the detection of DCIS is rapidly increasing, especially due to non-palpable forms.
2. Not all forms of DCIS develop into invasive cancer, but if a patient has carcinoma in situ, she is more likely to develop invasive cancer than a woman without DCIS.
3. High histological grade DCIS is more aggressive and has a higher invasive potential than low histological grade DCIS.
4. The frequency of regional metastasis in carcinoma in situ does not exceed 1-2%, so lymphadenectomy for most patients is unnecessary.
5. The success of the treatment of in situ carcinoma depends on the choice of the optimal amount of treatment, which is based on a careful assessment of prognostic criteria and an assessment of the risk of recurrence.

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General information

Lobular carcinoma in situ (DR in situ)

Lobular carcinoma (DR) in situ carries a 1% lifetime risk of developing bilateral breast cancer.

DR in situ is a potential precursor to infiltrating breast cancer under unusual conditions (pleomorphic lobular carcinoma in situ).

The generally accepted approach is surveillance through lifelong clinical and radiographic studies.

Bilateral prophylactic mastectomy appears to be an operative alternative; hereditary factors may influence this choice. Unilateral mastectomy is not used for in situ DR.

Chemoprophylaxis with tamoxifen or raloxifene can reduce the subsequent incidence of breast cancer by 50% or more.

Radiation therapy and axillary lymphadenectomy play no role in the treatment or diagnosis of patients with lobular carcinoma in situ.

Ductal carcinoma in situ

Most of the cases ductal carcinoma (PR) in situ is detected mammographically as an accumulation of microcalcifications, however, the volume of microcalcifications can lead to an underestimation of the severity of the lesion.

Stereotactic trepanobiopsy is the preferred diagnostic method for non-palpable masses detected by mammography.

Total mastectomy (TM) regarded as radical method treatment with a mortality subsequently associated with the tumor, equal to 0-1%.

Organ-preserving surgery (OSS) on the breast are an alternative treatment for limited PR in situ.

The completeness of the resection should be verified by radiography and histological examination.

The addition of adjuvant radiotherapy to SSI is based on prognostic factors affecting the incidence local recurrence (MR).

Tumor excision alone may be an appropriate treatment in select cases of small, well-differentiated tumors, achieving tumor excision within healthy tissue (clinical trial under consideration).

Axillary lymphadenectomy is not indicated for ductal carcinoma in situ, but for large, poorly differentiated PP in situ sentinel lymph node biopsy (SLNB) avoids reoperation in case of detection of metastases.

Approximately 50% of all cases of MR are infiltrating cancers with a 10-year tumor-specific mortality reaching 15% in infiltrating cancers.

The administration of tamoxifen can be considered as a measure to reduce both the risk of recurrence on the side of the tumor and cancer on the opposite side.

Lobular carcinoma in situ

DR in situ is an occult, non-infiltrating lesion that grows from the lobules and terminal ducts of the breast. While the true incidence of lobular carcinoma in situ has not been established due to the absence of clinical and radiographic evidence, a 2.6-4-fold increase in its incidence is attributed to an increase in the frequency of screening mammography, as well as better recognition of this pathological condition.

With increasing knowledge of the natural development of in situ DR, doctors have now begun to consider this disease a risk factor for breast cancer, rather than a progenitor tumor. For this reason, along with lifelong observation, a conservative approach was introduced into practice, accompanied by widespread recognition.

Bilateral mastectomy continues to be offered to patients as a form of surgical prophylaxis, but is an over-treatment because most women do not subsequently develop cancer.

The results of the NSABP P-1 and P-2 trials demonstrated a significant reduction in the incidence of breast cancer with the use of estrogen receptor modulators (tamoxifen and raloxifene) in patients at high risk, including those suffering from lobular carcinoma in situ. This approach represents an effective alternative to observation or bilateral mastectomy.

natural development

In the treatment of in situ DR, the fact that the risk of subsequent development of infiltrating cancer leads to oncological mortality is of importance. The relative risk of developing infiltrating breast cancer from baseline among the general population is estimated at 3-4.2 times.

Lobular carcinoma in situ carries a 23–30% risk of subsequent cancer development 15–20 years after diagnosis, whereas in situ LC has a 30–50% chance of developing cancer 10–15 years, highlighting the difference between the two. two pathological processes by the time of their development.

In addition, it seems that the incidence of contralateral breast involvement in in situ DR is higher, and that subsequent malignancies are either lobular or ductal.

Based on a recent analysis of Surveillance, Epidemiology, and End Results (SEER, Surveillance, Epidemiology and final results), it can be argued that infiltrating lobular carcinoma is diagnosed at a proportionally higher rate (23.1%) in patients with lobular carcinoma in situ than in the general population (6.5%).

Infiltrating ductal carcinoma still retains a leading position (49.7%) among subsequently developing malignant breast tumors detected after in situ diagnosis of DR.

The occurrence of infiltrating ductal carcinoma and the same risk for both breasts, combined with the fact that most patients with in situ DR do not develop infiltrating breast cancer, supports the hypothesis that in situ lobular carcinoma is a greater risk factor rather than precancerous breast changes.

Treatment

Until recently, surgical removal of in situ DR diagnosed by trepanobiopsy has been controversial. A growing body of evidence supports a significant increase in the incidence of in situ ductal carcinoma or infiltrating cancer after in situ DR removal and atypical lobular hyperplasia, similar to atypical ductal hyperplasia (APH), led to the recommendation surgical removal each of these lesions.

Achieving repeated excision of tumor removal within healthy tissue (clean resection margin) is of no clinical significance due to the proven multifocal and bilateral nature of lobular carcinoma in situ.

Given that in situ DR is a risk factor for breast cancer, close follow-up with lifelong medical examinations is recognized as the current standard of care. The fact that women with in situ DR, compared with women with in situ PR, are 5.3 times more likely to develop infiltrating lobular carcinoma and 0.8 times less likely to develop infiltrating ductal carcinoma may, however, , raise some doubts about the status of a precursor in DR in situ.

Surveillance for lobular carcinoma in situ includes at least annual mammography, clinical breast exams at 6 and 12 month intervals, breast self-examination, and diagnostic studies according to indications.

Magnetic resonance imaging (MRI) of the mammary glands in patients at high genetic risk shows promising results in the detection of clinically and mammographically hidden lesions, but has a similar rate of false positive results as mammography.

Bilateral prophylactic mastectomy with or without immediate reconstruction remains an option for a subgroup of patients with in situ DR. High-risk patients who are indicated for surgery include those with an additional risk based on family history or carriers of genetic abnormalities of the BRCA1/BRCA2 genes.

Patients who are unwilling or unwilling to accept a lifetime risk of 1% per year of later cancer, or who are unable to maintain follow-up, may also be considered eligible for surgery.

Partial mastectomy with radiation therapy does not currently play a role in treatment. In addition, lymphadenectomy of the axillary lymph nodes is not necessary, since lymph node metastases occur in less than 1% of patients.

Data from the NSABP P-01 Prevention Study included 826 patients with in situ DR with a mean follow-up of 55 months. Among women taking tamoxifen, compared with those receiving placebo, there was a 56% reduction in the incidence of infiltrating breast cancer.

In the NSABP P-02 (STAR) study, raloxifene was found to be as effective as tamoxifen in reducing the incidence of breast cancer. But in patients treated with raloxifene, the risk of non-infiltrating breast cancer was not statistically significantly increased.

A decrease in the risk of thromboembolism and cataracts and a statistically insignificant trend towards a decrease in the incidence of uterine cancer were observed in the raloxifene group. These chemoprophylaxis strategies offer therapeutic alternatives that combine the two extreme forms of management of such patients - observation and bilateral mastectomy.

In the upcoming NSABP P-04 study, high-risk postmenopausal women, including patients with lobular carcinoma in situ, will be randomly assigned to receive either raloxifene or an aromatase inhibitor as a chemopreventive drug.

Exodus

Evidence from observational studies shows that life-long oncological mortality on the background of observation alone is 7% with a risk of developing infiltrating cancer of 1% per year. However, a more recent long-term study has demonstrated a significantly lower risk (1%) of death.

Against the background of the use of chemoprophylactic agents, this risk can be further reduced. Bilateral prophylactic mastectomy results in an approximately 90% reduction in the incidence of subsequent breast cancer with negligible cancer mortality, but for most women, in whom the condition will never progress to infiltrating cancer, it is an excessive measure.

Ductal carcinoma in situ

PR in situ of the mammary gland is the proliferation of malignant cells of the ducts and acini of the mammary gland, which do not penetrate beyond the basement membrane of the epithelium of the ducts. The widespread use of high-definition mammography screening has increased the in situ diagnosis of ductal cancer by a factor of ten over the past twenty years.

This type of tumor accounts for approximately 20% of all mammary tumors detected by mammography. Since screening has become a priority for the national health system, there is hope that this trend will continue.

Historically, this poorly understood type of breast tumor was treated primarily with mastectomy. Increasing the frequency of application organ-preserving therapies (AML) in infiltrating cancer has increased the movement towards similar management of in situ PR, but there are only limited data on the natural development of PR in situ that can be used to inform treatment decisions.

Ductal carcinoma in situ is the most rapidly growing group of breast tumors. In 2003, more than 56,000 new cases were diagnosed in the US. Most of them are non-palpable and were detected mammographically.

As with in situ tumors, in situ PR, lacking the ability to grow and metastasize, does not express a fully malignant phenotype. Mastectomy is considered as a method of radical treatment, cancer mortality in this case is 0-1%. However, infiltrating local recurrence after AML carries the risk of increased mortality from breast cancer.

Clinical picture

Previously, PR in situ presented as a palpable mass, bloody or serous nipple discharge, or Paget's disease. With the introduction of high-resolution mammography, almost 90% of in situ PB cases were detected at the stage of clinically hidden formations in the form of accumulations of microcalcifications (76%), soft tissue thickening (11%), or both (13%).

While mammography is an excellent diagnostic tool, its specificity in differentiating between benign and malignant lesions is only 50-60% and can often underestimate tumor extent.

Such microcalcifications are usually acneiform necrosis that becomes clearly visible in grade III lesions. Indeterminate or pleomorphic calcifications may also be a manifestation of ductal carcinoma in situ.

Microcalcifications can also be benign fibrocystic changes, such as sclerosing adenosis, and PR in situ is detected only incidentally and is not accompanied by the occurrence of microcalcifications.

Ultimately, it is important that the biopsy sample, regardless of the method of obtaining it (fine-needle or trephine biopsy), is X-rayed, and the pathologist determines whether PR in situ is associated with microcalcifications.

Preoperative examination

Diagnostics

Imaging therapies are essential for both diagnosis and treatment. Stereotactic breast trephine biopsy is recommended as the first step in the diagnosis of non-palpable mammographic changes.

Due to technical limitations, in the case of a small volume of the mammary glands or extremely superficial or deep lesions, stereotaxic biopsy is not possible for all lesions.

When using stereotaxic biopsy, several trepans (size 9-11, ideally with a vacuum aspirator) should be prepared to ensure quality samples of microcalcifications are obtained. If all microcalcifications are removed, then the wire clip should be left as a marker in order to later determine the localization of the formation and remove it.

Complete surgical excision of such formations often leads to an overestimation of the degree of APH to cancer (both PR in situ and infiltrating ductal carcinoma) in 10-50% of cases and PR in situ to infiltrating cancer in 10-15% of cases.

When stereotaxic biopsy is not possible, or when histological findings suggest atypical ductal hyperplasia or PR in situ, an open guidewire biopsy is required. This will allow accurate diagnosis and breast preservation in patients diagnosed with ductal carcinoma in situ only.

Pathological histology

The histological classification of PR in situ is slowly being implemented in practice. Traditionally, it is based on structure, with two main categories: acneiform and non-pimple (sieve, micropapillary, papillary and solid).

Acne formations show marked necrosis, tumor cells have pleomorphic nuclei and a higher frequency of mitoses. Non-acneic types usually have a low degree of nuclear polymorphism and do not have severe necrosis.

In acne lesions, microinfiltration is more common, angiogenesis is more pronounced, and the rate of proliferation is higher. Pathologists have recently proposed new classifications based on the degree of nuclear polymorphism and the presence or absence of necrosis, perhaps better reflecting the prognostic factors that guide treatment.

Imaging methods for examining the mammary glands

When using standard mammographic projections, tumor volume is often underestimated, and magnified images are critical in assessing microcalcifications. With multiple (foci close to the index lesion) lesions, treatment with organ-preserving interventions is possible, while multicentric lesions (foci located in different quadrants of the breast) adversely affect the success of organ-preserving interventions.

Holland reported that most tumors are multifocal and not multicentric. Well-differentiated ductal carcinoma in situ is more likely to show a multifocal pattern than poorly differentiated tumors (70% vs. 10%).

Contrast-enhanced MRI shows promising results in revealing the prevalence and distribution of PR in situ in the mammary glands. MRI may be particularly useful in evaluating multicentric residual tumors or in occult infiltration, thus assisting in surgical management.

Surgical treatment options

Surgical treatment of in situ PR is based on the results of imaging studies, certain patient characteristics and histological examination biopsy specimens, usually obtained by imaging-guided biopsy.

Surgical methods include mastectomy with or without immediate reconstruction or excision within healthy tissue followed by observation (rarely) or adjuvant radiotherapy to the breast area.

Mastectomy (simple total) remains the most aggressive surgical treatment for in situ PR and the standard against which all other treatments are judged. Indications for mastectomy include: a multicentric tumor with two or more foci, diffuse calcifications that give the impression (or confirmed) of malignancy, and cases of preservation of tumor cells along the edge of the resected tissue after repeated surgical excision.

Patient factors that prevent the use of radiotherapy form the relative indications for mastectomy and include a history of disease connective tissue with vascular disease, prior breast irradiation, or chest and pregnancy. Mastectomy provides the greatest reduction in the risk of local recurrence, but may represent an overuse. surgery in most patients with small masses detected by mammography.

Indications for SSI include mammographically detectable in situ ductal carcinoma or localized, palpable masses without multicentricity or diffuse microcalcifications. The decision regarding radiotherapy in addition to organ-sparing interventions is also based on prognostic factors affecting local recurrence and those factors that may be affected by radiotherapy.

Critical factors in preoperative management include an assessment of the patient's needs and expectations for breast preservation. Treatment should be tailored to patient preference and the understanding that risk management is limited to local tumor removal.

While AML achieves better cosmetic outcomes than mastectomy, patients must accept the higher risk of local recurrence that accompanies organ-sparing treatments. Approximately 50% of local recurrences after AML for PR in situ are infiltrating cancer and may lead to reduced survival in patients who initially underwent organ-sparing therapies.

K.I. Blenda, M.U. Buhler, A. Xendes, M.G. Sarah, O.D. Gardena, D. Wang

site - BEAUTIFUL AND HEALTHY BREAST

Ductal breast cancer in situ- ductal carcinoma in situ, DCIS. is a common form of non-invasive breast cancer. The risk of developing ductal cancer in situ in women is the same as the risk of developing invasive cancer. Risk factors for the development of ductal cancer: no pregnancy in a woman, late pregnancy (there is after 30 years), early onset of menstruation, late onset of menopause, a hereditary factor - a case of breast cancer in first-degree relatives (mothers, sisters, daughters), a long period ( more than 5 years) replacement hormone therapy, especially with combination therapy with estrogen and progesterone, the presence of abnormal genes responsible for the development of breast cancer (BRCA1 or BRCA2).

Diagnosis of ductal breast cancer in situ

Diagnosis ductal breast cancer in situ not dangerous to a woman's life. This is a non-invasive form of cancer and it represents its earliest stage - stage 0, which is sometimes even called "precancer". Yes, this is cancer, this is uncontrolled cell growth, but this growth is noted only in the lumen of the milk ducts and does not go beyond them. Although this form of cancer is non-invasive, there is always a risk that it will later develop into invasive cancer - that is, one that spreads to normal breast tissue. From 25 to 50% of women who have undergone surgical treatment (without radiation therapy) for ductal carcinoma in situ have a chance to "earn" invasive breast cancer in the future.

In most cases, these recurrences occur 5 to 10 years after in situ detection of ductal carcinoma. However new cancer mammary gland can develop even later - after 25 years! It usually occurs at the same site as ductal carcinoma in situ. This new cancer can be either non-invasive or invasive. Therefore, the main goal of treating ductal carcinoma in situ is to reduce the risk of developing cancer in the future. There are three grades of ductal carcinoma in situ:

• low degree,
• average degree,
• High degree.

Low to moderate differentiation means that ductal carcinoma in situ cells closely resemble normal mammary ductal cells or have atypical ductal hyperplasia. The average degree of differentiation is sometimes referred to as moderate. These two grades are distinguished by a tendency towards a low cell growth rate.

Women with low- or moderate-grade ductal carcinoma in situ have a higher risk of developing invasive breast cancer in the future (after 5 years) compared to women without ductal carcinoma in situ. But compared to women with high-grade ductal carcinoma in situ, they have a much lower risk of developing new cancer or recurring in the first place.

A low degree of differentiation can manifest itself in several types of structures:

• Solid (solid) structure - cancer cells completely fill the lumen of the milk duct.
• Latticed structure - there are gaps between the clusters of cancer cells (like holes in Swiss cheese). ◦Papillary structure - the cells in the duct are arranged in the form of a fern leaf.

Highly differentiated - Highly differentiated ductal carcinoma in situ is characterized by rapid cell growth. Women with high-grade ductal carcinoma in situ have a very high risk of developing invasive breast cancer, either at the time of detection of ductal carcinoma in situ or in the future. in addition, these patients have an increased risk of early tumor recurrence (within 5 years). Sometimes highly differentiated ductal carcinoma in situ is called "comedo" (acne) due to appearance. They are dead cancer cells that form inside the tumor. The reason of that - fast growth tumors, as a result of which some cells "do not receive" nutrients.

Diagnosis of ductal carcinoma in situ

Usually, ductal breast cancer in situ does not show up and is not detected by physical examination. However, a small number of women may experience a tumor-like formation or some kind of discharge from the nipple. Most often, ductal carcinoma in situ is detected on mammography. The fact is that the “old” cancer cells, dying, do not have time to be completely utilized. As a result, this area is impregnated with calcium salts (the so-called calcification) - microcalcifications are formed. These microcalcifications just come to light on the mammogram.

If the doctor considers the results of mammography suspicious for cancer, the next stage of diagnosis is a biopsy. For ductal carcinoma in situ, two minimally invasive biopsies are performed (more invasive methods are not performed for ductal carcinoma in situ):

• Fine needle aspiration biopsy- at the same time, a thin long needle is inserted into the thickness of the area of ​​\u200b\u200bthe breast tissue suspicious for cancer and a small amount of tissue is “pumped out” (aspiration) with a syringe. After this procedure, no scars remain.
• Core biopsy - In this case, a larger needle is inserted and more tissue is taken from suspicious areas. Before inserting a thick needle, a small incision is usually made in the breast code. Of course, after it there is a small scar, which after a few weeks is almost invisible.

After receiving tissue samples, they are examined under a microscope. Usually, the amount of tissue that is taken during a biopsy is enough to perform tests for the presence of hormone receptors or determine the status of HER2. The biopsy procedure is performed for the purpose of diagnosis, and not to remove a cancerous tumor. This requires more surgery.

Surgical treatment of ductal breast cancer in situ

The most common treatment for ductal carcinoma in situ is to perform a lumpectomy operation - removal of a breast tumor followed by a course of radiation therapy.

Lumpectomy - partial removal of the breast for ductal cancer

Other treatments may be used, such as lumpectomy without radiation therapy or mastectomy, which may be either insufficient or too aggressive. Everything, of course, depends on individual characteristics. Among the surgical interventions for ductal carcinoma in situ, the following are commonly performed:

• Lumpectomy refers to a organ-sparing operation and consists in the removal of the entire area of ​​ductal carcinoma in situ in the mammary gland. Even if cancer cells are found in this area, but there is no tumor, the entire area where they are found is removed.
• Repeated resection (excision) - this type of surgical intervention is used when, after lumpectomy, cancer cells are found in the edges of the excised tissue.

In some cases, ductal breast cancer in situ can only be detected by mammography or ultrasound, but not palpable. In such cases, "localization" of the tumor is performed before the operation. To do this, under the control of X-ray or ultrasound, a needle is inserted into the suspicious area, through which tissue is excised. Sometimes MRI may be required for such localization.

Mastectomy - complete removal of the breast for ductal cancer

When the breast is completely removed, a mastectomy is performed. Mastectomy is recommended in case of:

• large ductal carcinoma,
• in case of a pronounced family predisposition to breast cancer,
• in case of detection of abnormal genes responsible for the occurrence of breast cancer.

In these cases, a mastectomy is used, which reduces the risk of developing invasive breast cancer in the future. Whether organ-sparing surgery is possible in your case depends on factors such as the size of the ductal carcinoma in situ, how many areas of the breast are affected by ductal carcinoma in situ, and the “cleanliness” of the excision margins.

If you have multiple areas of your breast affected by ductal carcinoma in situ, some doctors automatically recommend a mastectomy. The reason for this is that so far there are no studies that would confirm the same effectiveness of organ-preserving operations as mastectomy in such cases. The fact is that such research is not so easy to conduct. It is impossible to take a group of patients with a similar situation, and offer half of them a organ-preserving operation, and the other half - a complete removal of the mammary gland and then compare the results.

However, if ductal carcinoma in situ is detected in several areas of the breast, this does not mean that there is only one way out - mastectomy. If you really want to save your breasts, you need to talk to your doctor. When breast-conserving surgery may be better than a mastectomy:

• A woman has two small ductal carcinomas in situ, located very close to each other in one of the areas of the breast, and removed with "clean" edges. In this case, it is possible to use an organ-preserving operation - lumpectomy followed by radiation therapy. Mammography after surgery can confirm that the area of ​​cancer has been completely removed.
• A woman has two small ductal carcinomas in situ in different areas of the breast, with no other features (based on high-quality mammography and MRI). In this case, an organ-preserving operation can also be applied. In this case, two lumpectomy operations are performed, and sometimes repeated tissue excision may be required. Mammography after surgery can confirm that the area of ​​cancer has been completely removed. After the operation, a course of radiation therapy is performed, while only complete irradiation of the breast is performed.

When the choice is not so obvious and further evaluation of the choice of operation is required:

• Ductal carcinoma in situ is small, but there are many positive excision margins (i.e., detection of cancer cells in the margins). In this case, repeated excision of the edges is performed. If the edges of the excised tissues are still not “clean” (positive), then another re-excision is performed.
• Ductal carcinoma in situ is moderate in size and has many positive resection margins after lumpectomy or re-excision. In this case, further research is needed before deciding which type of surgery is right for you in this situation.

When a mastectomy may be better than breast-conserving surgery:

• Ductal carcinoma in situ involves the entire breast or occupies a large area or several areas of the breast.
• A woman has an abnormal breast cancer gene (BRCA1 or BRCA2) with concomitant ductal carcinoma in situ. In this case, even if the tumor is small, the operation of choice is a mastectomy.
• Pathological examination revealed ductal carcinoma in situ, occupying a large area of ​​the breast, as well as positive edges of the excised tissue, even if only a medium-sized tumor is detected on mammography. In addition, mammography may reveal microcalcifications throughout the breast tissue.
• MRI reveals an extensive lesion that extends beyond the ductal carcinoma in situ, which was identified on biopsy. This means that before the MRI, a dye was injected into the veins, which accumulated in a certain area.
• With the help of biopsy and radiological methods of diagnostics, pathological zones of the mammary gland were revealed.
• The woman had a medium to large tissue removed, and a highly differentiated ductal carcinoma in situ was found.
• A woman has tissue removed from medium to big size, with many positive excision margins noted. in such a situation, repeated excisions are unrealistic.

In all these situations, as you can see, ductal carcinoma in situ occupied a fairly large part of the breast. Therefore, it is necessary to remove the entire area in order to ensure that all ductal carcinoma in situ is removed. However, simply removing this area leaves a woman with very little breast tissue. In this case, a mastectomy greatly increases the chance that the tumor is completely removed. And reconstructive surgery after a mastectomy can return a woman to the shape of her breasts. By the way, there are women who, after a mastectomy, do not even want to reconstructive surgery. The addition of antiestrogen and radiation therapy to the treatment of ductal carcinoma in situ may slightly improve the outcomes of surgical treatment.

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