Breast Cancer

1. Breast Cancer Igor Galaychuk, MD, DSc Professor, Surgical Oncologist Chief, Department of Oncology and Radiology, Ternopil State Medical University, Ternopil, Ukraine

2. TNM as a logical model in cancer diagnosis Diagnostic procedures: - from simple to complex - from noninvasive to invasive

3. Diagnostic procedures: T • Breast cancer (T): Examination Palpation Mammography Ultrasonography CT Biopsy (FN, core) Cytology/Histology

4. Diagnostic procedures: N • Breast cancer (N): Palpation Ultrasound FN Biopsy/cytology Sentinel node biopsy/histology “Bethsabee au bain”, Rembrandt van Rijn

5. Diagnostic procedures: M • Breast cancer (M): Skin Contralateral breast and lymphnode areas CT (lung, liver) Bone scintigraphy RT-PCR Biopsy

6. TNM as a logical model in cancer diagnosis Making the clinical diagnosis: Carcinoma of the right breast T4N1M0, stage III

7. Sarcoma of the right breast

8. MammographsMETALTRONICA

9. Mammorgaphy with biopsyBYM 3D» Точность наведения +/- 1 мм

10. Digital mammography • Позволяет выполнять снимки как традиционным, так и цифровым способом • Возможность доработки существующих систем • Рабочая область: 220.8 x 176 мм • Полное разрешение:4384 x 3488 пикселей (размер пикселя 50 μм) • Режим малой дозы: 2192 х 1744 пикселей (размер пикселя 100 μм) • Динамический диапазон:14 bit

11. MRI breast tumor imaging • MRI

14. Advanced carcinoma

15. Inflammatory Breast Cancer

16. Schema of clinical syndrome Tender, granular swelling Microscopic aspect. Stunted lobules in proliferating fibrous stroma Fibrocystic Disease

17. Fibrocystic Disease: Adenosis Adenosis is characterized by the development, in one or both breasts, of multiple nodules, varying from 1 mm to 1 cm in size and usually distributed about the periphery of the breast, creating a nodular breast with a saucerlike edge. The affected mammary tissue contains dense fibrous tissue, numerous cysts, and foci of epithelial proliferation. Lobule formation is considerably distorted. Some of the terminal tubules form solid plugs of basal cells, which, on cross section, appear as duct adenomas. • Other tubules have greatly enlarged lobular structures, which are penetrated by dense strands of fibrous tissue, giving the appearance of an orderly proliferation of small ductules and acini, known as sclerosing adenosis. The incidence of cancer in patients with fibrocystic disease and accompanying ductal proliferative changes is approximately twice as high as is the incidence in the general female population.

18. Fibrocystic Disease: Adenosis

19. Benign Fibroadenoma and Intracystic Papilloma The fibroadenoma, the most common benign mammary tumor of the female breast, usually occurs in young adult women. The typical presentation is a firm, well circumscribed, nodular, freely mov­able, gradually enlarging mass. On excision, the tumor appears as a lobular mass and consists of well-developed ducts surrounded by marked overgrowth of periductal connective tissue. The growth of fibroadenoma is rapid in early adolescence, in pregnancy, or toward menopause, when estrogenic secretion is increased.

20. Benign Fibroadenoma and Intracystic Papilloma Benign intracystic papillomas are fleshy epithelial growths occurring within a mammary duct or a dilated acinus, usually at or near menopauses in the central zone of the breast. They cause either a sanguinous discharge from the nipple or a lump associated with moderate tenderness. Intracystic papillomas are encapsulated tumors that ( ontain branching epithelial) projections and rest on a fibrous stalk. Multiple papillomas may occur in one or both breasts.

21. Tumor ulcerated through skin Sarcoma Giant Myxoma and Sarcoma Giant mammary myxoma, also known as phyllodes tumor or cystosarcoma phyllodes, is a fibroadenoma that typically occurs near menopause and grows to large size. The tumors are heavy, massive, nobulated, fleshy growths with cystic areas; they remain encapsulated and moveable. Microscopically, the lesions are composed of myxomatous and fibrous connective tissue lined by epithelial cells and containing abundant stromal cells. Most of these tumors behave in a benign fashion. Mammary sarcoma is rare among the mammary tumors. Most of these sarcomas are fibrocellular lesions arising in the stroma of the breast or from the stroma of preexisting fibroadenomas. The lesions are characterized by rapid growth, large size, firm consistency, and, commonly, ulceration of the skin, with fungation of the mass. Tumor in right breast Giant myxoma

22. Giant Myxoma and Sarcoma

23. Infiltrating Carcinoma • Approximately 15% to 30% of mammary carcinomas are in situ, and 70% to 85% are invasive. Approximately 80% of invasive lesions are infiltrating ductal carcinoma (scirrhus carcinoma or carcinoma simplex). They present as a palpable mass and may be associated with nipple retraction. Grossly, these are dense, yellowish-white, stellate, irregular masses with a gritty consistency.

24. 2005 Breast Cancer Observatory • Breast Cancer: trends in the next years • Breast cancer will gain acceptance as a genetic disease. Technology will detect more mutations, competition will start among available testing technologies. • Research will tackle the issue of interactions between tumour and stroma and normal tissues, looking for the new targets therapies. • Renewed interest in the value of local control ( DCIS).

25. Infiltrating Carcinoma • Microscopically, the tumor cells have a relatively uniform size; exhibit prominent, hyperchromatic nuclei; grow in small nests or cords; and are accompanied by growth of fibrous tissue producing the scirrhus feature of the lesions. Invasive lobular carcinoma (5-10% of breast carcinomas) tends to be multicentric in the same breast, to involve both breasts at a high frequency (approximately 21 and to be hard to detect because of a diffusely invasive pattern. Prognosis is influenced by growth pattern of the tumor; degree of organization and cellular differentiation; expression of various gene products, including estrogen receptors and BRCA1 and BRCA2; and the presence of regional axillary lymph node and distant metastases

26. Fulminant Carcinoma • Inflammatory or acute fulminant carcinoma usually presents as a rapidly widening area of inflamed skin. The dermal inflammation usually correlates with retrograde spread of the cancer cells through the lymphatics of the skin. The skin is reddened, edematous, and rough, producing the characteristic orange peel effect. The carcinomatous spread is accompanied by a localized and systemic inflammatory process with low-grade fever, increased leukocyte count, and enlarged axillary lymph nodes. The most frequent site of local recurrence of breast cancer is the scar in the chest wall, followed by the axilla and the supraclavicular regions.

27. Fulminant erysipeloid cancer Carcinoma forming along surgical wound Recurrent cancer Fulminant Carcinoma

28. Circumscribed Forms of Adenocarcinoma • Approximately one fourth of mammary carcinomas have features of well-differentiated adenocarcinomas. These lesions include papillary adenocarcinomas, carcinomas with gelatinous, mucoid degeneration, and comedocarcinoma, a type of intraductal carci­noma that forms plugs and circumscribed rings of carcinoma cells in preexisting ducts. These lesions tend to bulge out from the breast rather than retract inwardly as with the infiltrating carcinomas. Skin and axillary node involvement occur much later in the course than with infiltrating scirrhous carcinoma. The tumors typically progress slowly and often reach large size. The majority are detected and removed by mastectomy before metastasis occurs. The lesions may have central foci of necrosis or hemorrhage.

29. Mass clinically presenting in left breast Mass seen in cross section of breast Circumscribed Forms of Adenocarcinoma

30. Paget Disease of the Nipple • Paget disease of the nipple is produced by carcinomatous invasion of the nipple or areola and the mouths of the larger ducts by large malignant cells with hyperchromatic or vesicular nuclei and pale staining cytoplasm. Usually, involvement of the nipple precedes the detection of a small primary tumor in the breast. The diseaseis occasionally bilateral. The involved nipple has a red granular or an exudating crusted appearance and eventually undergoes ulceration. Eventually, a hard mass, which is often associated with enlarged axillary lymph nodes, is palpable.

31. Eczematous type Ulceration type Paget Disease of the Nipple

32. Assessment of tumour characteristics to guide therapy choice will become increasingly common and accurate. • Systemic therapies will continue to become less toxic, the usage of cytotoxic chemotherapy in patient with small, node negative breast cancers will decrease. • Use of trastuzumab (Herceptin) and studies of Avastin will expand quickly and dramatically. Taxanes will be monitored.

33. The issue of treatment duration and maintenance of response will be tackled separately for endocrine responsive and endocrine non-responsive tumours. • Competition and cross-fertilization will increase between partial breast (PBI) and whole breast irradiation (WBI). • The real impact of post mastectomy irradiation will be challenged, biological response modifiers will be back. • Formal accreditation of breast units will start in Europe through a codified process including site visits and with the full participation of advocates (Europa Donna).

34. View of a Medical Oncologist and a Clinical/Translational Researcher • New prognostic factors such as the 70-gene profiler and the Oncotype DX will be prospectively validated in very large adjuvant breast cancer trials. • Lapatinib and Bevacizumab will be the next targeted therapies to be tested in the breast adjuvant setting, with the possibility of Lapatinib taking the place of Trastuzumab. • Further efforts will be made to understand and overcome mechanisms of resistance to chemo, endocrine and biological therapies. • Medical oncology will be recognized as a specialty in more countries, and patients will demand that their cancer care is delivered by cancer specialists in specialized units.

35. View of a Breast Surgeon and a Clinical Researcher • Affirmation of intraoperative radiotherapy. • Extension of sentinel node biopsy. • Possibility of preoperative application of BRCA tests which may modify surgical options. • Tailored oncoplastic surgery. • Increased use of surgical trials.

36. 1976- Multidisciplinary teams 1994 - Multiskills required 1999- Breast surgeons specialists 2007 Accreditation of breast surgeons 2007 Accreditation of breast units+ additional team members Training sites Quality indicators for breast cancer care 2007 World Cup 2007

37. Advances in breast cancer management Partial breast irradiation; 5 trials ongoing Awareness and application of reconstructive techninques to avoid deformity Lipofilling: autologous purified fat grafting

38. View of a Medical Oncologist and a Clinical/TranslationalResearcher • Continued reduction in the use of adjuvant chemotherapy in women with ER+ breast cancer with emphasis on identifying patients who derive a substantial benefit. • Ongoing focus on breast cancer subtypes, and growing understanding of heterogeneity within subtypes (e.g. differences among HER2 positive breast cancer).

39. Continued focus on angiogenesis inhibitors and their role in breast cancer treatment. • Continued focus on HER2 inhibition and agents that can work with and/or in place of trastuzumab. • Growing interest in targeted therapies for basal-like breast cancer. • Growing understanding of the need to consider long term treatment strategies to minimize risk of disease recurrence for women with hormonally sensitive disease.

40. Conclusions • Gene profiling + tumour subtyping • Lapatinib + bevacizumab • Angiogenesis inhibitors • Less chemotherapy • Patients in trials + accreditation • Sentinel node • Partial breast irradiation + intraoperative radiotherapy • More oncoplastic surgery