BREAST CARCINOMA INSITU

INSITU CARCINOMA BREAST MANAGEMENT

1. Nabeel Yahiya INSITU CARCINOMA BREAST

2. DCIS LCIS PAGETS DISEASE OF NIPPLE INTRODUCTION

3. Its incidence is increasing due to over diagnosis by screening mammogram Considerable controversy regarding optimal management Ranges from observation to bcs to mastectomy with and without adjuvant treatment INTRODUCTION..

4. neoplastic process that is confined to the ductal system of the breast and lacks histologic evidence of invasion These cells neither disrupt the basement membrane nor involve the surrounding breast stroma . lacks the ability to metastasize and is confined to the breast DCIS

5. ductal cells ductal carcinoma In situ (DCIS) Invasive ductal carcinoma

6. Before the use of screening mammography, DCIS typically presented as a palpable mass or nipple discharge. An invasive component commonly was found, and pure DCIS rarely was encountered. The widespread use of mammography now routinely detects DCIS <1 cm in diameter results in breast cancer-free survival rates that approach 100% CLINICAL FEATURES

7. Ninety-five percent of new cases of DCIS present with mammographic abnormalities microcalcifications are most typical asymmetric densities identified in 10% dominant masses in 8% abnormal galactograms (performed for evaluation of nipple discharge) in 6%.

8. Linear and branching calcifications frequently are associated with high-grade DCIS and necrosis, whereas fine and granular calcifications are associated more commonly with low-grade Initial evaluation should include magnification views that allow for complete characterization of mammographic findings and determination of the need for biopsy

9. DCIS MAMMOGRAM

10. The extent of the lesion as determined mammographically may be used as a guide for excision Ultrasonography , digital mammography, and magnetic resonance imaging all have the potential to be helpful in the management of DCIS but have yet to be proven as an acceptable substitute for mammography in screening

11. Traditionally, classification of DCIS has followed its architectural or morphologic appearance The five subtypes of DCIS are Comedo Solid Cribriform Micropapillary papillary PATHOLOGY

12. it is common to encounter a mixture of subtypes within the same specimen Less common subtypes Apocrine Neuroendocrine signet-cell cystic hypersecretory carcinoma clinging DCIS

13. features that should be documented for each case of DCIS nuclear grade, presence of necrosis, polarization, and architectural patterns margin status, lesion size, extent of microcalcifications , and correlation between specimen x-ray and mammographic findings

14. Unicentric (one area only) Multicentric (two distinct areas separated by more than 4 cm) Continuous (extension along ductal system without gaps) Discontinuous or multifocal (two or more areas separated by <4 cm). Faverly et al.s classification

15. recognized association between the presence of DCIS and the subsequent increased risk of developing an invasive breast cancer presence of shared identical genetic abnormalities between DCIS and synchronous invasive breast cancer demonstrates a clonal relationship of biologic progression DCIS a precursor lesion?

16. The estrogen receptor is present in 70% of DCIS Rate of expression is higher in low-grade lesions (90%) than in high-grade lesions (25%). This association with histologic grade is reversed for the rate of overexpression of HER2/ neu proto-oncogene and the p53 tumor suppression gene.

17. An occult microinvasive tumor (<1mm) may be seen with some cases of DCIS Occult microinvasive tumors are most common in patients with DCIS Lesions that are >2.5 cm in diameter Presenting with palpable masses or nipple discharge, High-grade DCIS or comedonecrosis

18. A primary consideration in the natural history of DCIS is the risk of progression to invasive carcinoma The few published long-term follow-up studies of DCIS after only biopsy document an overall incidence of subsequent invasive carcinoma of more than 36% Women with DCIS in one breast are at risk for a second tumor (either invasive or in situ) in the contralateral breast Natural History of DCIS

19. The goal of treatment with DCIS eradication of the initial cancer prevention of local recurrence, with particular emphasis on the prevention of invasive breast cancer TREATMENT

20. The recommended workup and staging of DCIS includes: history and physical examination bilateral diagnostic mammography MRI (optional) pathology review tumor ER determination

21. MASTECTOMY BCS BCS n RT OPTIONS

22. Mastectomy was the standard treatment of DCIS through the first four decades Mastectomy is a highly effective treatment for DCIS, with a locoregional control rate of 96% to 100% cancer-specific mortality rates of 4% or less MASTECTOMY VS BCS

23. Many retrospective studies suggest that the rates of local or regional recurrence are significantly lower after mastectomy than after breast-conserving surgery but there have been no significant differences in overall survival No prospective randomized trials comparing mastectomy to breast-conserving surgery for DCIS

24. Prospective randomized trials have shown that the addition of whole breast irradiation to a margin-free excision of pure DCIS decreases the rate of in-breast disease recurrence, but does not affect survival OR distant metastasis-free survival. BCS ± RT

25. Whole breast irradiation after breast-conserving surgery reduces the relative risk of a local failure by approximately one half. The current challenge is to identify women with DCIS whose risk of an ipsilateral breast tumor recurrence (primarily invasive) with breast-conserving surgery, with or without radiation

26. Age Women 40 years of age or younger with DCIS have been reported to have ipsilateral breast tumor recurrence rates of approximately 50% in retrospective series n EORTC prospective randomized trial. Most of the prospective randomized trials suggest that increasing age is associated with a decreased risk of ipsilateral breast tumor recurrence in patients treated with conservative surgery alone or conservative surgery and radiation. FACTORS PREDICTING RECURRENCE

27. Methode of detection detection of DCIS solely by mammography was associated with a lower risk of ipsilateral breast tumor recurrence when compared with clinical detection with symptoms such as a palpable mass or bloody nipple discharge

28. Size Clinical assessment of tumor size includes measurements of a palpable mass, the dimensions of the mammographic abnormalities, including calcifications and/or a mass In the EORTC and South Sweden prospective randomized trials, increasing clinical size was associated with an increased risk of ipsilateral breast tumor recurrence in patients treated with conservative surgery alone but not those treated with conservative surgery and radiation

29. In the NSABP B-17 randomized trial the ipsilateral breast tumor recurrence rate was correlated with the extent of calcifications on the mammogram, both in women treated with conservative surgery alone or conservative surgery and radiation In patients having calcifications, a postexcision mammogram before radiation or observation is essential to assure the removal of all malignant-appearing calcifications

30. Multifocality Multifocal DCIS has been associated with an increased risk of ipsilateral breast tumor recurrence in different prospective randomized trials when compared with unifocal disease in patients treated with conservative surgery alone or conservative surgery and radiation

31. Resection margin status Positive margins of resection have been associated with an increased risk of ipsilateral breast tumor recurrence in the NSABP B-17, EORTC, and the NSABP B-24 trials Negative margins greater than or equal to 2 mm were associated with a decreased risk of ipsilateral breast tumor recurrence when compared with those less than 2 mm Critical margin < 1mm and >10mm

32. High nuclear grade and the presence of necrosis have been associated with an increased risk of ipsilateral breast tumor recurrence in patients undergoing conservative surgery These factors have had less of an impact on ipsilateral breast tumor recurrence rates in patients undergoing conservative surgery and radiation

33. breast density is an increased risk of ipsilateral breast tumor recurrence in women with DCIS.

34. a scoring system with four categories: Age Size Margins nuclear grade combined with necrosis University of Southern California/Van Nuys Prognostic Index

35. Van Nuys Prognostic Index Parameter 1 Point 2 Points 3 Points Size <15mm 16-40mm >40mm Grade 1/II 1/II Necrosis III Margin 10mm 1-9mm <1mm Age >60 40-60 <40 4,5, 6 = Lumpectomy Alone 7, 8, 9 = Lumpectomy + Radiation 10, 11, 12 = Mastectomy 2003 Update PMID 14682107 -- "An argument against routine use of radiotherapy for ductal carcinoma in situ." (Silverstein MJ, Oncology (Williston Park). 2003 Nov;17(11):1511-33; discussion 1533-4, 1539, 1542 passim.) 

36. Total scores ranging from 4 to 12. SCORE 4-6 7-9 10-12 BCS ONLY 4% 40% 87% BCS +RT 4% 30% 38%

37. The investigators concluded that patients with scores of 4 to 6 were candidates for wide excision alone scores of 7 to 9 for excision and radiation scores of 10 to 12 for mastectomy.

38. The reproducibility of this system has been questioned by a number of investigators in retrospective and prospective studies. Inaccuracies in calculating the score could result in overtreatment or undertreatment

39. There is retrospective evidence suggesting that selected patients have a low risk of in-breast recurrence with excision alone without breast irradiation. Retrospective study of 215 patients with DCIS treated with lumpectomy without radiation therapy, endocrine therapy, or chemotherapy, the recurrence rate over 8 years was 0%, 21.5%, and 32.1% in patients with low-, intermediate- or high-risk DCIS BCS ONLY IN LOW RISK?

40. A multi-institutional, nonrandomized, prospective study of selected patients with low-risk DCIS treated without radiation was studied Although an acceptably low ipsilateral recurrence rate was observed in the low-/intermediate-grade arm of the study at 5 years 7-year ipsilateral recurrence rate in this group of patients was considerably higher

41. An analysis of specimen margins and specimen radiographs should be performed to ensure that all mammographically detectable DCIS has been excised. In addition, a post-excision mammogram should be considered POST SURGERY MANAGEMENT

42. Axillary dissection is not recommended for patients with pure DCIS

43. ROLE OF TAMOXIFEN NSABP B-24 trial women with DCIS who were treated with breast-conserving therapy were randomized to receive placebo or tamoxifen . 13.6 years median follow-up, the women treated with tamoxifen had a 3.4% absolute reduction in ipsilateral in-breast tumor recurrence risk No differences in overall survival (OS) were noted

44. lumpectomy plus radiation (category 1) total mastectomy, with or without reconstruction (category 2A) when persistent positive margin or multicentric tumors lumpectomy alone followed by clinical observation (category 2B). TREATMENT SUMMARY OF DCIS

45. history and physical examination every 6 to 12 months for 5 years and then annually as well as yearly diagnostic mammography. FOLLOW UP

46. characterized by multicentric breast involvement Consists of loose, discohesive epithelial cells that are large in size, variable in shape, and contain a normal cytoplasm to nucleus ratio The extent of involvement of the lobular lumen ranges from simple filling to moderate-to-severe distention with extension into the adjacent extralobular ducts LCIS

47. LCIS represents <15% of all noninvasive breast cancer The majority of women are premenopausal at diagnosis, with an average age of 45 years There are no clinical or mammographic indicators that are characteristic of LCIS In excisional biopsy specimens, DCIS or invasive carcinoma are frequently identified even when LCIS is the sole histologic entity seen on core biopsy

48. multicentric distribution in up to 90% of mastectomy specimens bilateral involvement in 35% to 59% LCIS cells are commonly estrogen-receptor positive overexpression of c-erbB-2 and p53 are uncommon The loss of e- cadherin is often observed

49. The presence of LCIS is considered a marker of increased risk for the subsequent development of invasive (usually ductal ) carcinoma greatest for high-grade or more extensive lesions This risk appears to be nearly equal for both breasts RISK FOR INVASIVE CARCINOMA

50. Depends on whether it is associated with another malignancy (DCIS or invasive carcinoma) Approximately 10% of early-stage breast cancers have an associated component of LCIS MANAGEMENT

51. treatment approach is to manage the breast according to the dominant malignant histology (DCIS or invasive carcinoma) and disregard the presence of LCIS. it is not necessary to pursue additional surgery to obtain clear margins for LCIS If LCIS is the sole histologic diagnosis, treatment recommendations range from conservative to radical

52. Earlier days due to high frequency of contralateral breast involvement it was justified to do contralateral biopsy and even bilateral mastectomy Observational studies after wide local excision alone have led to a better understanding of the natural history of this condition, and a more conservative approach is now commonly practiced

53. In patients with LCIS as the sole histologic diagnosis, the most widely accepted clinical practice is close observation with regular physical examination and mammographic surveillance There is no role for radiotherapy in the management of LCIS. Unilateral mastectomy both inadequate and illogical. Bilateral prophylactic mastectomy is likely excessive prophylactic approach in high-risk patients is to consider the use of tamoxifen

54. characterized by the presence of Paget's cells that are located throughout the epidermis Paget's disease is a rare entity representing <5% of all breast cancer cases) typically diagnosed in the fifth or sixth decade. Synchronous bilateral and male Paget's disease have been reported Paget's disease is associated with an underlying malignancy in more than 95% Paget's Disease

55. the disease originates from the underlying in situ or invasive disease There is histologic evidence of intraepithelial extension, immunohistochemical studies, and evidence suggesting that the epidermal keratinocytes release a motility factor, heregulin that results in the chemotaxis of Paget's cells that migrate to the overlying nipple epidermis

56. Itching and burning of the nipple and areola. There is a slow progression toward a crusting eczematoid appearance that can extend to the periareolar skin. If neglected, bleeding, pain, and ulceration can occur . Alternatively, Paget's disease can be asymptomatic and present as a pathologic finding after incidental surgical removal of the nipple areolar complex CLINICAL FEATURES

57. A palpable mass is detected in approximately 50% of patients at diagnosis more than 90% of cases this will be an invasive carcinoma. if no palpable mass is detected, 66% to 86% will have an underlying DCIS. These associated malignancies are usually located centrally, Mammographic findings are frequent in the presence of a palpable mass but normal mammograms are reported in as many as 50% of cases

58. clinical evaluation includes bilateral breast examination mammography, and biopsy to confirm the diagnosis of Paget's disease and to fully evaluate the extent of the associated malignancy The prognosis does not dependent on the diagnosis of Paget's disease, but rather on the associated malignancy

59. Management of Paget's disease continues to evolve. Mastectomy was employed in the past but this has been increasingly supplanted by breast-conserving treatment The infrequent occurrence of this disease entity the range of disease presentations variable extent of surgical resection has made the evaluation of treatment options difficult

60. The combination of limited surgical resection and postoperative radiotherapy appears to be the most practical breast-conserving approach Surgical resection should include the nipple areolar complex with microscopically clear margins surrounding both the Paget's disease and the associated malignancy

61. THANK YOU