Minimally invasive diagnostic procedures in patients with inflammatory breast cancer and negative imaging test

Authors: Saribekyan E.K., Stepanov S.O., Guts O.V.

PA Hertsen Moscow Oncological Research Institute, Russian Federation

ABSTRACT

We have studied peculiarities and problems in order to determine whether or not cancer is present in “diffuse” forms of a breast cancer cases (IBC, for example) when breast imaging techniques usually have not found breast cancer. The most effective technique that takes a sample for cancer verification is US –guided core needle biopsy. We prefer take tissue samples from the most suspicious areas of a breast with indirect tumor sights and also taking samples from areas of a breast where the breast cancer detected very often – in upper lateral and central areas of a breast. Vacuum-assisted breast biopsy has many advantages in comparison with traditional core needle biopsy and fine-needle aspiration in order to get reliable result when imaging is not clear.

Key words: “diffuse” breast cancer, minimally invasive diagnostic, breast biopsy

Correspondence to: Erik Karlovich. E-mail: mammolog3@yandex.ru

Introduction. The breast cancer takes the first place among malignant tumors at women. Diffuse form of breast cancer (such as IBC) accounts for 15-17% of all breast cancer cases [4]. Diffuse form of breast cancer is characterized as enlargement one of the breast combining with thickening of the skin and redness. Inflammatory breast cancer is an edematous affection with skin changes like an orange peel and nonpalpable lesion with diffuse structure, fast growing tumor mass. IBC grows and spreads so quickly and it is harder to treat successfully this type of breast cancer [1, 7]. The most common symptom in patients with IBC is nonpalpable lesion without clear boundaries.

IBC is an especially aggressive form of breast cancer. The features of clinical manifestation of “diffuse” breast cancer with mastitis symptoms can lead to diagnostic errors and delay to initiation of treatment.

The last decade has witnessed the rapid development of imaging techniques and methodologies in cancer diagnostic. There are ultrasound, digital x-ray mammography, CT, MRI, biopsy under X-ray or ultrasound guidance [2,6]. Modern diagnostic equipment allows us to detect breast cancer 4mm diameter or less, and take the cells for cancer verification using fine-needle biopsy. In this case, each method has the features and limitations, depending on the physical properties of breast tissue and the nature of cancer [3, 9].

X-ray mammography is more informative in women older than 40 years with the prevalence of involutive processes in the breast glands and fatty tissue. Marked glandular component and the hyperplastic tissue more typical for young women, and these peculiarities reduced the possibility of X-ray visualization of structures that are "lost" in the hyperplastic tissue array. In this situation ultrasound becomes more informative.

CT scan (compared with ultrasound and mammography) shows the tumor more precisely located in retromammarnuyu space and the extent of tumor on the chest wall that is important in the planning of surgical intervention and treatment. CT clearly diagnosed thickening of the structural pattern of the breast, skin thickening in cases of IBC, increasing the size of one breast. However the restructuring of the surrounding tissue and tumor hypervascularity in breast more accurately visualized with mammography [10]. The method of MRI has high sensitivity (100%) and specificity (90%). MRI performed in the tomograph with the magnetic field intensity of 1.0 T. The study was conducted before and after intravenous administration of contrast agent [8].

The patient is placed on the abdomen and breasts are placed in special mammographic "coil" which create the necessary compression. The diagnosis of cancer put upon detection of nodules, if the lesion is intensely and diffusely increased during the first two minutes after administration of contrast agents. Information about using MRI in diagnostic of IBC and other diffuse forms of breast cancer in the world literature is insufficient for the specific recommendations [5, 11]. In addition, using of MRI is limited by high cost, complexity and duration of the study, the presence of “coils” only for the same size breasts. Performing a biopsy under MRI – guidance has become possible in recent years; however it is technically more difficult manipulation compared with biopsy under X-ray or US– guidance.
Thus, “diffuse” forms of cancer without clear boundaries of the tumor especially in combination with fibrous tissue may be difficult in diagnosis despite using modern imaging techniques. It extends the period of investigation and delayed the start of appropriate treatment. Increasing the number of outpatient visits the patient also contributes to high financial costs of medical institutions.

Materials and methods.

Studied the results of the survey in 26 patients in whom the presence of direct and indirect symptoms of breast cancer did not allow to visualize and verify the tumor during the preliminary examination. The study was conducted in Hertsen Moscow Oncological Research Institute for the period 2007- 2010. All patients had a clinical picture of IBC. They complained of enlargement and protrusion of the quadrants or the entire breast, pain and discomfort in the breast, feeling the bloating in the breast. Most of the patients (20 women) were examined in connection with suspected infiltrative-edematous symptoms such as swelling, skin changes like an orange peel combined with warmth and edema . In 8 patients we identified and verified metastases in the axillary lymph nodes. Immunophenotyping showed that metastasis spread from breast cancer (three of patients – without detected lesions in the breast after total medical inspection). 6 patients submitted to Hertsen Moscow Oncological Research Institute after due to presence suspicious sites identified after medical examination (palpation, mammography and ultrasound). Age of patients ranged from 30 to 72 years (mean age was 51.4 years).

All the patients before treatment in Oncological Research Institute and during the initial survey were made mammography and ultrasound. In addition, CT scans performed in 7 patients, MRI – in 4 patients. All patients were attempts to verify the diagnosis. We took samples of tissue for morphological studies in the areas where presumably could localize the tumor. We used well known biopsy techniques: fine needle aspiration biopsy with / without US- guidance (26 patients), vacuum− assisted biopsy under X-ray guidance (3), open surgical biopsy of the skin in the areas of swelling of the skin (4), sectoral resection (3). The number of biopsies in the manipulation of a single method was from 1 to 3, repeated biopsies were performed only after fine-needle biopsies in 12 people.

In connection with the problem of verification of the diagnosis, all patients are directed to the study of minimally invasive procedures, which performed the final diagnostic procedure.

Equipment of examination room includes a vacuum biopsy device "Mammothom", equipped with paddle handles with needle gauge 11G and 14G in the assembly "Endo-Surgery Etikon, Inc.", corporation "Johnson and Johnson" (USA, Mexico), spring loaded biopsy systems BARD, ultrasound scanners SONOLINE with Siemens Medical Solution accessories (USA).
To obtain tissue samples for histological examination we made biopsy in areas with indirect signs of tumor under US - guidance, and arbitrarily in places the most frequent localization of IBC - in the upper outer and central quadrants. The choice of needle gauge for biopsy (from 14 to 11G) was determined according to the size of the breast, expression changes in the breast and the physical density of the breast tissue. Samples of the breast tissue after biopsies was labeled, numbered and reflected in the scheme which was annexed to the direction of the histological examination. This technique called multipoint arbitrary and automatic vacuum -biopsy under US- navigation.

We considered as a possible presence of indirect signs of tumor areas with hyperechogenicity, abnormal vascularity in the Doppler, the concentration of tubular structures, US and clinical (inspection, palpation) picture of the differences with the healthy breast. We paid special attention to areas with severe fibrosis. Our experience has shown that the application of medical imaging techniques mostly do not notice tumor located below the array of fibrous tissue.
Selection of the most frequent localization is based on a study carried out in Hertsen Moscow Oncological Research Institute. We studied the frequency of tumor in IBC cases, composing the vast majority in the structure of the “diffuse” form of breast cancer. In 288 patients we examined the localization of the breast tumor in breast quadrants, quadrants borders and central areas. The most frequent localization was the upper-outer quadrant - 29,5% ± 2,7, central areas - 17,0%± 2,2.

Case report.
Patient ZH.N.S., 71 years,

Diagnosis: Cancer of left breast cancer stage IIB, T2N1M0.

From the history: In July 2010 patient found changes in the left breast as a protrusion in the upper areas of the breast. She was examined in Hertsen Moscow Oncological Research Institute As a result of a comprehensive examination (medical inspection, palpation, ultrasound, mammography) we obtained fibrosis. Mammography report (17.08.10): in the left breast the border of the upper quadrant is marked with a restructuring of the seal in the center of the fibrosis type. The right breast is without focal pathology. However despite the mammography and US results, the clinical did not allow rejecting diagnosis of the breast cancer.

Picture1. Inspection of the breasts.

Swelling in upper and central quadrants of the left breast.

Hematoma after fine-needle biopsy.

Picture 2. Mammography Picture 3. Mammography

of the left breast. of the right breast .

Fibrosis structure. Without focal pathology .

Picture 4. US picture with Doppler of the left breast.

Picture 5. US picture of the left breast.

The patient was redirected to ultrasound examination into for microinvasive multipoint vacuum-biopsy under US-guidance. After histological examination was diagnosed lobular carcinoma. 30/08/10 surgical operation: radical mastectomy on the left. Histological conclusion № T 48729-47/op on 06.09.10:

tumor in the central parts of the site without clear boundaries sizes 3.5Х2.5х3 cm. Iinfiltrative lobular carcinoma grade 2 (7 points) with the presence of tumor embolls in the lumen of lymphatic vessels. 4 lymph nodes - lobular cancer metastasis without invasion beyond the capsule. Postoperatively, radiation therapy is carried out and courses of chemotherapy according to the scheme CAF. At follow-up examination one year after the operation - with no signs of recurrence.

The results of treatment.
Histological examination of material obtained by multipoint arbitrary vacuum-biopsy under US-guidance in all these cases established to define diagnosis. In two cases, after an automatic biopsy performed with uninformative material we made vacuum-biopsy. Repeated manipulation after vacuum-biopsy did not needed. In 22 cases (84.6%) was verified breast cancer, in 2 patients was diagnosed fibrosis of the tissue, in 1 patient - chronic mastitis. In one patient the bright clinical picture of IBC (edema and redness of the skin of breast) was due to thrombosis of the veins extending from the subclavian vein. All cases of non-malignant changes were confirmed by the observation periods of 6 months and more. Histological forms of breast cancer: ductal cancer– 10 cases, lobular cancer – 5 cases, the combined ductal and lobular – 6 cases, intraductal cancer – 1case. The results of the various minimally invasive diagnostic methods are presented in Table 1.

Types of biopsies	Number of biopsies	Number of repeated biopsies	Cancer verification	Average number of tissue samples due to usual biopsy
Automatic biopsy	10	2	9 (90%)	5
Vacuum-biopsy	16	-	16 (100%)	4

Table 1.

Conclusion:
Due to examination of patients with diffuse form of breast cancer by medical imaging may be significant errors in diagnosis and complexity of cancer verification in cases with undetected tumor, despite the high spreading the process. The most difficult for diagnosis are cases of tumor in located in or under an array of severe fibrous tissue.
In cases of getting uninformative material after fine-needle biopsy the most effective method of obtaining tissue samples for verification is multipoint vacuum-biopsy of suspicious areas and biopsy sites the most frequent localization of “diffuse” cancer - in the upper-outer and central quadrants in the breast. Vacuum-assisted breast biopsy has many advantages in comparison with traditional core needle biopsy and fine-needle aspiration in order to get reliable result when imaging is not clear. But the final choice made by the specialist individually.
Manipulation should be performed highly skilled and experienced professional.

References.

1. Pak D.D., Saribekyan E.K. / Chapter "Tumors of the breast" in Russian Oncology Guide. Ed. V.I.Chissova, S.L.Daryalovoy. -M. LLC "Medical News Agency," 2008. - p.382-408.

2. N.V.Ponedelnikova, G.P.Korzhenkova, V.P.Letyagin, Ya.V.Vishnevskaya. Selecting the method of verification of palpable space-occupying lesions of the breast at the preoperative stage. Tumors of the female reproductive system. -2011 - N1- p.41-45.

3. Guidance in Radiodiagnostic techniques in evaluation of breast disease, edited by prof. G.E. Trufanova - "ELBI-Petersburg" - St. Petersburg. - 2009. - p. 192-281.

4. Condition of cancer care in Russia in 2009. Edited by V.I. Chissov, V.V. Starinskiy, G.V. Petrova. Moscow, 2010.

5. Fisher W., Baum, F., Lyuftner-Nagel C./Chapter “Medical Imaging”, Diseases of the breast, edited by B.I.Dolgushina. M. MEDpress-Inform, 2009. p.10-190.

6. V.P. Harchenko, N.I. Rozhkova/Chapter “Edema syndrome of the breast”, Radiology diagnostic of breast diseases, treatment and rehabilitation. - 2000. - Issue 3. - P.113-114.

7. Chhikvadze T.V./”Edematous breast cancer: clinical features, diagnosis, treatment”. Russian Journal of Oncology. 2008. -N5- p.49-54.

8. Doshi A., Wedam S.B., Thomasson D.M. et al. Dynamic contrast enhanced MRI (DCE-MRI) as a potential predictor of clinical response in patients with inflammatory breast cancer (IBC)// ASCO Meeting Abstracts.- 2005.- V.23.- P.584.

9. Kushwaha A.C., Whitman G.J., Stelling C.B. et al. Primary inflammatory carcinoma of the breast: retrospective review of mammographic findings// AJR Am J Roentgenol.- 2000.- V.174(2).- P.535-538.

10. Mogavero G.T., Fishman E.K., Kuhlman J.E. Inflammatory breast cancer: CT evaluation// Clin Imaging.- 1992.- V.16(3).- P.183-186.

11.Yang W.T., Le-Petross H.T., Macapinlac H. et al. Inflammatory breast cancer: PET/CT, MRI, mammography, and sonography findings// Breast Cancer Res Treat.- 2007. –V.109(3).-P.417-26.