INSITU CARCINOMA BREAST MANAGEMENT

1. Nabeel Yahiya

2.  DCIS
 LCIS
 PAGETS DISEASE OF NIPPLE

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

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

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%

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

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

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).

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

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

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

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

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

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

25.  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.

27.  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

28.  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.

29.  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

30.  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 EORTCand 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

31.  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

32.  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

33.  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

34.  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

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

36.  a scoring system with four categories:
 Age
 Size
 Margins
 nuclear grade combined with necrosis

37. 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.)

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

39.  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.

40.  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

41.  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

42.  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

43.  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

44.  Axillary dissection is not recommended for patients
with pure DCIS

45.  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

46.  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).

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

48.  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

49.  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

50.  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

51.  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

52.  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

53.  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

54.  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

55.  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

57.  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%

58.  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

59.  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

60.  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

61.  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

62.  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

63.  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

64.  THANK YOU