Chest wall includes ribs,intercoaastal muscle, serratus anterior (Note: Invasion of dermis alone does not qualify as T4) Inflammatory carcinoma is a clinicopathol entity characterized bu diffused erythema and oeema of more tha 1/3 rd of skin of breast imaging revaeal adetectable mass n thickening of skin skin changes are due to tumor emboli within dermal lymphatics causing lymphdema
Clinically detected nodes are more than 1 cm with characteristic of macromets confirmed by fnac fnab
Clinical ,usg,ct but not lymhoscintigraphy
Micromets are 0.2 mm-2mm
• The designation pM0 is not valid; any M0 should be clinical. • If a patient presents with M1 prior to neoadjuvant systemic therapy, the stage is considered Stage IV and remains Stage IV regardless of response to neoadjuvant therapy. Stage designation may be changed if postsurgical imaging studies reveal the presence of distant metastases, provided that the studies are carried out within 4 months of diagnosis in the absence of disease progression and provided that the patient has not received neoadjuvant therapy. • Postneoadjuvant therapy is designated with “yc” or “yp” prefix. Of note, no stage group is assigned if there is a complete pathologic response (CR) to neoadjuvant therapy, for example, ypT0ypN
Photo of pagets pt
he committee recommended and described features that should be documented for each case of DCIS, thus separating out important pathologic components and providing a comprehensive evaluation of the pathologic findings. These features include nuclear grade, presence of necrosis, polarization, and architectural pattern(s). The committee extended its recommendations to include margin status, lesion size, extent of microcalcifications, and correlation between specimen x-ray and mammographic findings
including patients with DCIS involving 4-5 cm of disease or more than one area of the breast, those with a large tumor-to-breast ratio, those who should not receive radiation due to certain medical conditions or have received prior radiation therapy, and those for whom negative margins could not be achieved with BCS.35 Women who have a mastectomy for DCIS have a very low probability of recurrence in the treated breast, but remain at increased risk of developing DCIS or invasive breast cancer in the untreated (contralateral) breast. A study of 18,845 patients diagnosed with DCIS in 1973-1996 found that the cumulative risk of contralateral invasive or in situ breast cancer was 3% at 5 years, 6% at 10 years, 9% at 15 years, and 11% at 20 years.36 Women treated with unilateral mastectomy are followed with clinical breast examination and mammography to screen for DCIS or invasive cancers in the contralateral breast. Magnetic resonance imaging (MRI) of the breast may also be an option for women with a history of DCIS who are at high risk due to certain other risk factors.37
very low incidence of axillary metastases.157
RESULTS: updated The benefit of lumpectomy plus radiation was virtually unchanged between 5 and 8 years of follow-up and was due to a reduction in invasive and noninvasive ipsilateral breast tumors (IBTs). Incidence of locoregional and distant events remained similar in both treatment groups; deaths were only infrequently related to breast cancer. Incidence of noninvasive IBT was reduced from 13.4% to 8.2% (P = .007), and of invasive IBT, from 13.4% to 3.9% (P < .0001). All cohorts benefited from radiation regardless of clinical or mammographic tumor characteristics. CONCLUSION: Through 8 years of follow-up, findings continue to indicate that lumpectomy plus radiation is more beneficial than lumpectomy alone for women with localized, mammographically detected DCIS. When evaluated according to the mammographic characteristics of their DCIS, all groups benefited from radiation.
[52–55] (Figure 9). Figure 9: Diagram of NSABP-B17 trial. who were Tumor size was determined by mammogram, gross pathologic measurement, or clinical examination
2008) 1,046 patients with DCIS Lumpectomy ±50 Gy RT 5-year follow-up: RT reduced noninvasive LF 13→4% and invasive LF 9→3% (total LF: 22→7%). No difference on DM or OS
A mentioned, and an overview of results was reported by the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG).147
). (Table 55.3). Positive tumor margins were significantly associated with breast recurrence. margins to 11.5% with the addition of tamoxifen. In those with tumor
Women treated with unilateral mastectomy are followed with clinical breast examination and mammography to screen for DCIS or invasive cancers in the contralateral breast. Magnetic resonance imaging (MRI) of the breast may also be an option for women with a history of DCIS who are at high risk due to certain other risk factors.37
Several studies have addressed the rate of local recurrence after the various treatment options for DCIS [3, 4, 10, 14-17]. In the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-17 trial, local recurrence rates after breast-conserving surgery and radiation therapy were reported to be 7% at 5 years and 12% at 8 years [14, 17, 18]. The European Organization for Research and Treatment of Cancer (EORTC) trials confirmed reduced recurrence rates with radiation therapy, reporting 10-year local recurrence rates of 14.8% for the group treated with radiation and 26% for the group treated with lumpectomy alone (p < 0.0001) . The United Kingdom Coordinating Committee on Cancer Research (UKCCCR) study showed 5-year ipsilateral recurrence rates of 6% for the radiation therapy group versus 14% for the group with lumpectomy alone (p < 0.0001) [20Read More: http://www.ajronline.org/doi/full/10.2214/AJR.06.1281
Breast: Carcinoma in situ management
Carcinoma In Situ
Presented By: Dr Isha Jaiswal
Moderated By: Dr Ritusha Mishra
Date:10th March 2015
AJCC 2010 TNM STAGING OF CA BREAST*
• Primary Tumor
• Definitions for classifying primary tumor (T) are same for clinical &
Tx : Primary tumor cannot be assessed
T0: No evidence of primary tumor
Tis: Carcinoma in situ
• Tis (DCIS): Ductal carcinoma in situ
• Tis (LCIS) :Lobular carcinoma in situ
• Tis (Paget’s) :Paget’s disease of the nipple
*AJCC VII Cancer Staging Manual 2010 springer
T1:Tumor ≤2 cm in greatest dimension
• T1mic :Microinvasion ≤ 0.1 cm in greatest dimension
• T1a :Tumor > 0.1 cm but ≤0.5cm in greatest dimension
• T1b :Tumor > 0.5 cm but ≤1 cm in greatest dimension
• T1c :Tumor > 1 cm but ≤ 2 cm in greatest dimension
T2 :Tumor > 2 cm but ≤ 5 cm in greatest dimension
T3 :Tumor >5 cm in greatest dimension
T4 :Tumor of any size with direct extension to chest wall &/or skin
• T4a :Extension to chest wall, not including pectoralis muscle
• T4b :Edema (including peau d’orange) /ulceration/ satellite skin nodules
confined to same breast) (Dimpling & nipple retraction are not t4b)
• T4c: Both (T4a and T4b)
• T4d :Inflammatory carcinoma.
Regional Lymph Nodes
Definitions for classifying regional lymph nodes (N) are different for
clinical & pathologic classification.
Clinical lymph node classification based on clinical examination
&/or imaging studies such as USG,CT but excluding
Clinically detected nodes are more than 1 cm with characteristic of
macro metastasis confirmed by fnac or biopsy
pathological classification applies when lymph nodes are removed
surgically & examined histopathologically
Clinical Lymph Node Classification (cN)
Nx :Regional lymph nodes cannot be assessed
N0 :No regional lymph node metastases
N1 :Metastases to movable ipsilateral level I,II axillary lymph nodes
N2 : divided into N2a & N2b
• N2a :Metastases in ipsilateral level I,II axillary lymph nodes fixed to one another
(matted) or to other structures
• N2b Metastases only in ipsilateral internal mammary nodes in the absence of
axillary lymph node metastases
N3: divided into N3a,N3b &N3c
• N3a Metastases in ipsilateral infraclavicular lymph node(s) level III axillary
• N3b Metastases in ipsilateral internal mammary lymph node(s) and axillary
• lymph node(s)
• N3c Metastases in ipsilateral supraclavicular lymph node(s) irrespective of axillary
& internal mammary lymph node involvement
Pathologic Lymph Node Classification (pN)
pNx :Regional lymph nodes cannot be assessed (e.g., previously removed
or not removed for pathologic study)
pN0 :No regional lymph node metastases histologically
pN0 (i-): No regional lymph node metastases histologically, negative IHC
pN0 (i+): Malignant cells in regional lymph node(s) no greater than 0.2 mm
(detected by H&E or IHC including Isolated tumor cells)
pN0 (mol-) :No regional lymph node metastasis histologically,negative
molecular findings (reverse transcriptase polymerase chain reaction [RT-
pN0 (mol+) :Positive molecular findings (RT-PCR), but no regional lymph
node metastases detected by histology or IHC
pN1mi :Micrometastases (greater than 0.2 mm, and/or more than 200 cells,
but none greater than 2.0 mm)
pN1a :Metastases in 1-3 axillary l.ns, at least one metastasis greater than 2.0
pN1b : Metastases in internal mammary l.ns with micrometastases or
macrometastases detected by sentinel lymph node biopsy but not clinically
pN1c :Metastases in 1–3 axillary l.ns and in internal mammary l.ns with
micrometastases or macrometastases detected by sentinel lymph node biopsy
but not clinically detected
N2a: Metastases in 4-9 axillary l.n (at least one tumor deposit greater than 2.0
pN2b :Metastases in clinically detected internal mammary l.n in absence of
axillary l.n metastasis
pN3a :Metastases in 10 or more axillary l.ns (at least one tumor deposit
greater than 2.0 mm), or metastases to the infraclavicular (level III axillary
pN3b :Metastases in clinically detected ipsilateral internal mammary l.ns in
presence of one or more positive axillary l.ns,
or in more than three axillary l.ns and in internal mammary l.ns with
micrometastases or macrometastases detected by sentinel lymph node
biopsy but not clinically detected
pN3c :Metastases in ipsilateral supraclavicular l.ns.
Distant Metastasis (M)
M0 :No clinical or radiographic evidence of distant metastases
cM0(i+) :No clinical or radiographic evidence of distant metastases,
but deposits of molecular or microscopically detected tumor cells
detected in circulating blood, bone marrow, or other nonregional
nodal tissues, that are no larger than 0.2 mm in a patient without
symptoms or signs of metastases
M1 :Distant detectable metastases as determined by classic clinical
and radiographic means and/or histologically proved larger than 0.2
AJCC 7th Edition Staging for Breast Cancer
*T1 includes T1mi.
** T0 and T1 tumors with nodal micrometastases only are excluded from Stage IIA & are
classified Stage IB.
Carcinoma in situ
CIS represents non invasive cancer defined by confinement of
malignant cells within basement membrane
Widespread use of mammography has lead to an increase in
overall incidence of in-situ lesion
They differ in natural history, pathologic appearances, biologic
characteristics, clinical presentation & treatment
CIS of the breast (stage 0) includes
• Paget’s disease of the nipple
• Lobular carcinoma in situ (LCIS)
• Ductal carcinoma in situ (DCIS).
Cancer Facts & Figures 2015 Special Section:
Breast Carcinoma In Situ
In 2015, there will be an estimated 60,290 new cases of breast CIS
83% of them will be ductal carcinoma in situ (DCIS)
12% of them will be lobular carcinoma in situ (LCIS).
This year’s special section reviews breast carcinoma in situ, including
incidence rates and trends, risk factors, prognostic characteristics, and
*Cancer Facts & Figures 2015 American Cancer Society
• Paget’s disease is a rare entity
• represents <5% of all breast cancer
cases & associated with an
underlying malignancy in >95% of
• characterised by crusting &
eczematous appearance of nipple-
• characterized by presence of Paget’s
cells located throughout the
• Paget’s cells are large
,hyperchromatic, round/oval nuclei
with abundant cytoplasm found in
clusters or individually
Epidermotropic Theory of Paget's disease
• belief that the disease originates from underlying in situ or invasive ca
• also supported by histologic evidence of intraepithelial extension,
• IHC studies & evidence suggest that epidermal keratinocytes release a motility
factor heregulin-α, that results in the chemotaxis of paget’s cells that migrate to
overlying nipple epidermis.
• Age:5th -6th decade
• Gender: F>>M
(male Paget’s have been reported)
• Usually U/L
(synchronous b/l paget's have been reported)
• Symptoms include:
red, flaky,scaly rash which spread from nipple to
tingling, itching, burning, over the rash.
thin discharge may be present forming a crust as it
with more skin destruction, there may flattening of
bleeding, pain, and ulceration in advanced stage
Alternatively, can be asymptomatic and present as
pathologic finding after surgical removal of the
• palpable mass detected in 50% pts.at diagnosis: in >90% of
cases, this will be an invasive carcinoma.
• no palpable mass is detected: 66%- 86% will have an
• these associated malignancies are usually located centrally,
although they can occur elsewhere in the breast.
• Diagnostic Work Up Includes:
bilateral breast examination,
mammography, and biopsy
• Mammographic findings are frequent in the presence of a
palpable mass; however, normal mammograms are reported
in as many as 50% of case
Treatment of Paget's disease
The combination of limited surgical resection and
postoperative radiotherapy is 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.
Whole-breast radiotherapy is delivered with standard
a seven-institution collaborative review of 36 patients with Paget’s disease
without a palpable mass or mammographic density treated with local excision &
94% of patients underwent surgery
extent of surgical resection varied complete excision (69%), partial excision of
nipple–areolar complex & underlying breast tissue (25%), & biopsy only in 6%
The final margin status was documented as negative in 56%, positive in 6%, and
unknown in 39%.
all patients received median EBRT dose of 50 Gy (range, 45–54 Gy) to whole
97% of patients also received a boost to tumor bed,
median total dose of 61.5 Gy (range:50.4 –70 Gy).
median follow-up =113 months (range, 18 –257 months)
Actuarial local control rates for breast as only site of first recurrence were 91% at 5
and 87% at both 10 and 15 years.
Actuarial local control rates for breast recurrence, as a component of first failure,
were 91% ,83% and 76% at 5, 10, and 15 years, respectively.
4/36 patients (11%) developed first recurrence in treated breast only:2 were
DCIS only & 2 invasive with DCIS.
Two additional patients had a recurrence in breast as a component of first
No clinical factors were identified as significant predictors for breast
5-, 10- and 15-year actuarial rates for DFS was 97%
actuarial rates of OS was 93 at 5 years and 90% at 10 and 15 years
CONCLUSIONS. excellent rates of LC,DFS & OS at 10 and 15 years
following BCS and RT for Paget disease of the breast.
This study continues to support the recommendation of local excision and
definitive breast irradiation in the treatment of patients with Paget disease
presenting without a palpable mass or mammographic density
Lobular carcinoma in situ
• comprise 15% of in situ disease
• approximately 22-26% LCIS associated with DCIS or invasive
• not a precursor of invasive cancer instead, considered a marker
for increased risk of developing invasive breast cancer.
• Exception :Pleomorphic LCIS -linked to a higher risk of invasive
• Risk of development of invasive cancer is 20%–25% when
followed over a duration of 15 years
• risk appears to be nearly equal for both breasts & is greatest for
high-grade or more extensive lesions.
LCIS incidence and trends
• The incidence rate of LCIS was 3.9/100,000 women during
• peaks in women ages 50-59
• higher for non-Hispanic white women
• LCIS represent abnormal cells growing within the walls of the
• Pleomorphic LCIS: an aggressive variant that has a greater
potential for progressing to invasive cancer
• Multicentric (90% of mastectomy specimens)
• bilateral involvement (in 35%-59% of mastectomy specimens)
• ER/PR+, Her 2 nue negative
• loss of E-cadherin is often observed, and the absence of this
adhesion molecule may explain the growth pattern seen with
• (Vos CB, et al. E-cadherin inactivation in lobular carcinoma in situ of the breast:
an early event in tumorigenesis. Br J Cancer 1997;76:1131–1133.)
age: varies with race
extremely rare in men.
usually asymptomatic: no symptoms on clinical and
rarely may present as
• breast lump:.
• nipple discharge:
Diagnosis of LCIS
• no clinical or mammographic indicators that are characteristic
• often detected as
an incidental biopsy finding.
in excisional biopsy specimens ( dcis or invasive carcinoma are
frequently identified even when lcis is the sole histologic entity
seen on core biopsy)
The only definitive way to diagnose LCIS is by a breast biopsy
GOAL OF TREATMENT LCIS
• Treatment of LCIS emphasizes medical surveillance
and risk reduction strategies for both breasts rather
than local treatment, such as BCS plus radiation
Management of LCIS
LCIS : sole
medical surveillance and
risk reduction strategies
a/w another malignancy
(DCIS or invasive
manage the breast according to
dominant malignant histology
Management of LCIS: sole histologic diagnosis
Role of SURGERY
Local Excision & Subsequent Surveillance
Complete removal with negative margins is considered important
for more histologically aggressive pleomorphic LCIS.
unilateral mastectomy: inadequate and illogical.
Bilateral prophylactic mastectomy in high risk:
diffuse high-grade lesion
significant family history.
*Fisher ER et al. Pathologic findings from NSABP—12 year observations
concerning lobular carcinoma in situ. Cancer 2004;100:238–244
Medical surveillance recommendations
annual mammography and clinical breast exam every 6-12 months.
(National Comprehensive Cancer Network. Breast Cancer Screening and Diagnosis
Role of MRI in LCIS
In 2009, NCCN published guidelines reflecting a panel consensus opinion
that annual breast MRI can be considered in patients with LCIS.
three studies have been published evaluating the role of MRI in patients with
1. Friedlander LC, Roth SO, Gavenonis SC. Results of MR imaging screening for breast cancer
in high-risk patients with lobular carcinoma in situ. Radiology 2011;261(2):421–427.
2. Port ER, et al. Results of MRI screening for breast cancer in high risk patients with LCIS and
atypical hyperplasia Ann Surg Oncol 2007;14:1051–1057.
3. Sung JS, et al. Screening breast MR imaging in women with a history of lobular carcinoma in
situ. Radiology 2011;261(2):414–420
Each document revealed a small but defined 3.8% to 4.5% breast cancer
detection rate with MRI
cohort comprised of 182 women with LCIS who were enrolled in NSABP
Protocol B-17 but received no treatment other than lumpectomy.
Nineteen pathologic features were assessed & related to i/l breast tumor
recurrence(IBTR) & c/l breast tumor recurrence (CBTR) at a mean time 5 years.
Results were published at 5 years & updated at 12 years
2 invasive& 2 CIS
1invasive CBTR :lobular type
other mucinous carcinoma
1 non invasive CBTR were
1 CBTR were LCIS only.
NSABP B-17: results at 5 years
All IBTR occurred in same quadrant
9 were CIS & 4 invasive recurrences
All 4 invasive IBTR were lobular type
3 non invasive IBTR were pure DCIS
5 non invasive IBTR were LCIS only
1 non invasive IBTR were LCIS&DCIS
All examples tested were found to be c-erb B-2 negative, and estrogen receptor
and progesterone receptor positive.
results at median follow-up of 12 years.
• 26(14.4%) in-breast tumor recurrence (IBTR) rate
9 IBTRs (5% of the total cohort) were invasive carcinoma
17 (9% of the total cohort) were DCIS
• 14(7.8%) contralateral breast tumor recurrence rate.
• 10 CBTR (5.6% of total cohort) were invasive carcinoma
• Although the frequency of contralateral breast tumor recurrence rate was
less than that of IBTR, frequency of invasive contralateral breast tumor
recurrence rate (5.6% of total cohort) was similar to invasive IBTR (5% of
• Of note, all of the IBTR were documented to be at the site of the index
lesion except for one, characterized as pure LCIS, that was found at a
Both the American Society of Clinical Oncology (ASCO) and
NCCN recommend chemoprevention therapy
tamoxifen: for premenopausal women
tamoxifen or raloxifene: for postmenopausal women,
depending on other health conditions.
• (ref:Allred DC, Anderson SJ, Paik S, et al. Adjuvant tamoxifen reduces subsequent
breast cancer in women with estrogen receptor-positive ductal carcinoma in situ: a
study based on NSABP protocol B-24. J Clin Oncol. 2012;30: 1268-1273)
ASCO also lists exemestane, an aromatase inhibitor, as an
option in postmenopausal women; however, this is not FDA-
• (ref:Visvanathan K, Hurley P, Bantug E, et al. Use of pharmacologic interventions
for breast cancer risk reduction: American Society of Clinical Oncology clinical
practice guideline. J Clin Oncol. 2013;31: 2942-2962.)
• N = 13 388
• patients at elevated risk for breast cancer
>60 years old,
35–59 yrs with 5-year predicted risk of at least 1.66% based on Gail model,
history of LCIS
• Randomly assigned into 2 groups
• Group 1: (n = 6707) recieve placebo
• Group 2: (n = 6681) tamoxifen 20 mg/day for 5 yrs
*Fisher B, Costantino J, Wickerham DL, et al. Tamoxifen for prevention of breast cancer: report of the
National Surgical Adjuvant Breast and Bowel Project P-1 study. J Natl Cancer Inst 1998;90:1371–1388.
Tamoxifen reduced risk of :
invasive breast cancer by 49% (two-sided P<.00001)
non-invasive breast cancer by 50% (two-sided P<.002).
reduced occurrence of ER+tumors by 69%
no difference in occurrence of ER-tumors
age related decreased risk occurred in women
aged 49 years or younger (44%),
50–59 years (51%),
60 years or older (55%);
risk was also reduced in women with a history of lobular carcinoma in situ
(56%) or atypical hyperplasia (86%)
Side Effects In The Tamoxifen Group
rate of endometrial cancer increased in the tamoxifen group
risk ratio = 2.53
increased risk occurred predominantly in women aged 50 yrs or older
Cumulative rates of invasive endometrial cancer
rates of stroke, pulmonary embolism, and deep-vein thrombosis were
elevated in the tamoxifen group; these events occurred more frequently in
women 50 years or older
reduction in hip, radius (Colles’) & spine fractures
No increase in liver, colon,
rectal, ovarian or other tumors
No alteration in the average
annual rate of ischemic heart
NSABP-P2 STAR (vogel et al 2006).
Tamoxifen vs raloxifene
• 19,747 postmenopausal women at increased risk of breast CA
• Randomized to Tamoxifen 20 mg qd vs. Raloxifene 60 mg qd ×
• Incidence of invasive breast CA 0.4% both arms, but fewer
noninvasive cases (DCIS/LCIS) with Tamoxifen (0.15 vs.
• Raloxifene reduced risk of uterine cancer (absolute 0.7→0.5%)
cataracts,and thromboembolic events.
• Similar number of osteoporotic fractures, other cancers, stroke,
and heart disease.
Vogel VG, Costantino JP, Wickerham DL, et al. NSABP: prevention trials and endocrine
therapy of ductal carcinoma in situ. Clin Cancer Res 2003;9:495 S–501 S.
Ductal carcinoma in situ
• Constitute 80% of CIS
• DCIS is a precursor lesion to invasive ductal carcinoma
• It is confined to ductal system of breast lacks histologic
evidence of invasion into basement membrane & surrounding
• lacks the ability to metastasize
• axillary node involvement is rare (0% to 5%) and most likely is
associated with an undetected focus of invasive carcinoma.
Pathobiologic Events Associated with DCIS
majority of changes that give rise to cancer, including genetic changes, & loss of
normal cell-cycle regulation, occurred by the time DCIS is present
Most of clinical features of subsequent invasive cancer are already determined
although additional events, including tissue invasion and changes in surrounding
stroma characterize the invasive tumor
Natural History of DCIS
primary consideration in DCIS is the risk of progression to invasive
few published long-term follow-up studies after biopsy only document
overall incidence of subsequent invasive carcinoma of >36%. Most of these
subsequent malignancies occur within 10 years although as many as one-
third may develop after 15 years.
• (ref:betsill wl, rosen pp, lieberman ph, et al. intraductal carcinoma: long-term
follow-up after treatment by biopsy alone. jama 1978;239:1863–1867)
Women with DCIS in one breast are at risk for a second tumor (either
invasive or in situ) in the contralateral breast
rate at which such tumors develop is similar to that among women with
primary invasive breast cancer at approximately 0.5% to 1% per year.
• (ref:Habel LA, Moe RE, Daling JR, et al. Risk of contralateral breast cancer
among women with carcinoma in situ of the breast. Ann Surg 1997;225:69–75.)
• Traditionally, classification of DCIS has followed its
architectural or morphologic appearance.
• The five subtypes of DCIS are
Peak Age 60 -74 75 – 79
Race Caucasian Caucasian
Family History Yes Yes
Mammographic Density Yes Yes
Obesity No Yes
No children Yes Yes
Late age at childbirth Yes Yes
Hormone replacement No Yes
Risk factors for the development of DCIS are the same as
those identified for invasive carcinoma*
*Trentham-Dietz A, Newcomb PA, Storer BE, et al. Risk factors for carcinoma in situ of the
breast. Cancer Epidemiol Biomarkers Prev 2000;9:697–703.
• Before the use of screening mammography,
DCIS presented as a palpable mass/ nipple discharge.
invasive component commonly was found, and pure DCIS
rarely was encountered.
• The widespread use of mammography now routinely detects
DCIS <1 cm in diameter
• Studies have shown that the rate of screen-detected DCIS
increases with age
• The rate of DCIS detection increase from 0.56 per 1,000
mammograms among women aged 40 to 49 years to 1.07 per
1,000 mammograms among women aged 70 to 84 years.
Mammographic findings of DCIS
• 95 % present with mammographic abnormalities
• Most common finding is microcalcifications seen in 76%
• Noncalcified mammographic findings (24%) includes
asymmetric densities identified in 10%,
dominant masses in 8%,
abnormal galactograms in 6%.
Calcification in DCIS
• all forms of calcifications that that
can be related to DCIS. : Amorphous,
coarse, fine pleomorphic, fine linear
• Linear and segmental calcifications
are associated with DCIS in up to
80% of cases.
Linear and branching calcifications
associated with high-grade (DCIS).
Fine and granular calcifications
associated with low-grade DCIS
Role of MRI
• Size of lesion is underestimated in mammography by 1-2 cm
when compared with pathological specimen
• MRI now presents as the imaging modality with the highest
sensitivity to detect DCIS, particularly high-grade DCIS.
• MRI better establish the extent of DCIS, thus aiding treatment
• Lehman CD. Magnetic resonance imaging in the evaluation of ductal carcinoma in situ. J Natl
Cancer Inst Monogr 2010;(4):214–217.
• Berg WA, Gutierrez L, Nessairer MS, et al. Diagnositic accuracy of mammography, US, and MR
imaging in preoperative assessment of breast cancer.Radiology 2004;133:830–849
• In cases that present with nipple discharge and a negative
mammogram, galactography may be helpful in determining
the likelihood of underlying DCIS versus papilloma
Role of galactography
ACR-ASS-CAP-SSO 2006 practice guideline
• The role of other image modalities, especially MRI, has
yet to be established in DCIS.
• Berg found that MRI was more sensitive than
mammography and sonography in detecting DCIS;
however, disease extent was overestimated in 50% of
• The impact of MRI on clinical outcomes such as local
recurrence in the preserved breast remains to be
Goal of treatment: DCIS
• Eradication of initial cancer
• prevent progression to invasive/noninvasive cancer.
Breast Conservation for DCIS
• Breast conservation surgery (BCS) may consist of
quadrantectomy, wide excision, lumpectomy (local excision).
• A primary goal of BCS for DCIS is to achieve the best possible
cosmetic outcome along with negative margins
• microscopic complete excision is essential for optimal local
control in breast-conserving therapy for DCIS.
• 1 cm margin is considered adequate
• 1–2 mm post-BCS require re excision as up to 1/2 will have
• even in the group of DCIS cases who underwent a surgical re-
excision a 4-year local recurrence rate of 18% was observed
when these patients were treated with surgery alone.
Contraindications to BCT
• Repeatedly positive margins
• Multicentric disease ( >2 quadrants)
• Diffuse malignant calcifications on mammogram
• Prior RT to breast
• History of scleroderma
• Large tumor in small breast: cosmetically undesirable
Additional tests done after BCS*
• Specimen mammography
• Post excision mammography
• Frozen section analysis
• Complete histopathological assessment of
*Standard for the Management of Ductal Carcinoma In Situ of the BreastCA
Cancer J Clin 2002;52:256-276
• Specimen mammography of lumpectomy specimen
• Allows surgeons to asses the adequacy of excision
• Reduce the no of reexcisions required to achieve margin –ve resections
• less tissue excised : better cosmesis
• Reduces frequency of missed lesions: hard copy confirmation reduces
• Prolongs surgical procedure
• Increases cost
• False + & false - results
• Limited ability to predict margin status due to magnification &
• Discordance between SM & pathological & post excision mammography
Post excision mammography
• Done post excision & pre radiotherapy
• obtained to document complete removal of calcifications.
• can be performed as soon as the patient can tolerate
compression however, a large seroma may obscure small
• Magnification views taken( may show calcifications not
evident on nonmagnified views)
• It is used as a complementary means of assessing the
completeness of excision.
• If reexcision is performed for residual calcifications,
specimen radiography and a post-excision mammogram
should again be obtained to reassess the tumorectomy site.
Frozen section examination
• *Frozen sections should be avoided if possible especially on
lesions, which measure <1cm. in diameter
• Indicated when information is necessary for immediate
• reduction in the rate of reexcision
• Methodological difficulties
• Ductal carcinoma in situ is more difficult to identify in FSA
• small foci of microinvasion may be lost or rendered
uninterpretable by freezing artifact.
* Association of Directors of Anatomic and Surgical Pathology. Immediate management of
mammographically detected breast lesions. Am J Surg Pathol 1993;17:850-851
• Following should be included in the pathology report
presence/absence of necrosis
distance to excision margins/margin status
Calcification in the Tumour (or DCIS): Yes/ No
Estrogen Receptor Status: PR Status/Her-2 neu Status
risk factors for local recurrence after
breast-conservation therapy for DCIS
• Through multiple retrospective studies, several factors have
been identified that may be important in defining local
failure risk. These include
• patient age
• symptomatic presentation
• lesion size
• histopathologic subtype
• nuclear/cytologic grade
• central necrosis
• margin status
Mastectomy for DCIS
• Mastectomy is a highly effective treatment for DCIS
• locoregional control rate of 96% to 100%
• cancer-specific mortality rates of ≤4%.
• No randomized study has compared mastectomy with BCS for
• Data from some surgical series and large treatment registries
suggest that rates of local or regional recurrence are significantly
lower after mastectomy than after breast-conserving surgery,
• although there have been no significant differences in overall
Indications for total mastectomy
• If BCS is contraindicated
• Repeatedly positive margins after BCS
• patient desire. minimize the chance of ipsilateral recurrence
or for other reasons
• Recurrent disease
Age at diagnosis was strongly associated with the type of treatment received
younger women: more likely to undergo mastectomy.
53% pts younger than 40 underwent mastectomy
bilateral mastectomy 28%
unilateral mastectomy 25%
proportion of DCIS pts undergoing bilateral mastectomy has increased over the past 2
decades, from 2% of patients in 1998 to 8% in 2011.
Lymph node dissection in DCIS
• Axillary lymph node dissection & sentinel lymph node
mapping not routinely warranted
• 3-13% of patients with DCIS have isolated tumor cells in
sentinel axillary lymph nodes
• sentinel lymph node mapping may be used in selected
patients with a higher likelihood of occult invasive
those with extensive ds
those undergoing mastectomy
• Breast irradiation reduces the risk of subsequent invasive or
noninvasive carcinoma in the treated breast
• Four prospective randomized studies of excision only versus
excision plus breast irradiation for DCIS have been performed
• all have shown that the rate of local recurrence was reduced
with the addition of radiation
NSABP B-17 trial
EORTC 10853 trial
United Kingdom, Australia, and New Zealand (UK/ANZ)
Swedish Breast Cancer Group SweDCIS study
(Fisher et al.
first randomized trial which confirmed the effectiveness of
RT in decreasing local recurrence after lumpectomy with
negative resection margins in DCIS
• 813 pts. stratified by age (≤49 years vs. >49 years), DCIS versus DCIS plus
LCIS, method of detection, and whether an axillary dissection was
• Mean follow-up time was 90 months (range, 67 to 130).
• Of the patients enrolled, 83% had nonpalpable tumors
The updated analysis with 15-year follow-up showed a decreased cumulative
incidence of both invasive and non-invasive ipsilateral breast recurrences from
35% to 19.8% with the addition of radiation therapy.
The incidence of invasive ipsilateral breast recurrence was also decreased from
19.4 to 8.9% with the addition of radiation therapy to lumpectomy.
Increased LR with: +margins, moderate/marked comedonecrosis ,and
(Julien et al. 2000;
Bijker et al. 2006)
PATIENTS AND METHODS:
Between March 1986 and July 1996, 1,010 women were randomly assigned to
no further treatment (503 patients) or to RT(507 patients) after LE
analysis performed in August 2005, at median duration of follow-up: 10.5 years
The median age of the women was 53 years;
71% of them were mammographically detected.
Extent of free margins was not specified other than that DCIS should not be
present at microscopic examination of margins.
irradiation dose was 50 Gy in 25 fractions to the whole breast. No boost was
advised .Tamoxifen not recommended.
primary end points were both invasive and DCIS LR in the treated breast.
Secondary end points included metastasis, death, and contralateral breast
The 10-year LR-free rate was 74% in the group treated with LE alone compared with
85% in the women treated by LE plus RT
The risk of DCIS and invasive LR was reduced by 48% (P = .0011) and 42% (P =
Both groups had similar low risks of metastases and death.
The effect of RT was homogeneous across all assessed risk factors.
At multivariate analysis,
factors significantly associated
with an increased LR risk were
intermediately or poorly
cribriform or solid growth
treatment by LE alone
2x2 factorial designed randomised controlled trial.
Aim: to compare excision alone versus excision plus tamoxifen versus excision
plus radiotherapy versus excision plus radiotherapy and tamoxifen in completely
complete surgical excision was confirmed by specimen radiography and histology
tamoxifen was prescribed as 20 mg per day
radiotherapy was delivered through whole-breast tangential fields to a total dose of 50
Gy. Boost was not recommended
Between May, 1990, and August, 1998, 1701 patients recruited from screening
programmes were randomised to 4 arms
Arm 1: excision alone
Arm 2 : excision plus tamoxifen
Arm 3: excision plus radiotherapy
Arm 4:excision plus radiotherapy and tamoxifen
primary endpoint: incidence of ipsilateral invasive disease
median follow-up 53 months:
rates of all breast events were 8, 18, 22, and 6%, respectively.
When analysing those randomized to RT vs. no RT,
RT reduced LF (invasive or noninvasive) in ipsilateral breast from 14 to 6%
but there was no effect on the occurrence of contralateral disease.
Ipsilateral invasive disease was not reduced by tamoxifen but recurrence of
overall ductal carcinoma in situ (i/l & c/l )was decreased (hazard ratio
0.68 [0.49-0.96]; p=0.03).
Conclusion: Radiotherapy can be recommended for patients with ductal
carcinoma in situ treated by complete local excision; however, there is little
evidence for the use of tamoxifen in these women
Cusck J, Sestak I, Pinder SE, et al. Effect of tamoxifen and radiotherapy in women with locally excised
ductal carcinoma in situ: long-term results from the UK/ANZ DCIS trial Lancet Oncol 2011;12:21–29
median follow-up of 12.7 years.
addition of radiotherapy was demonstrated to reduce the risk of IBTR.
Of the 1,030 patients randomized between no radiotherapy versus radiotherapy, ipsilateral
IBTR was 19.4% versus 7.1%, respectively (p <.0001).
The addition of tamoxifen offered no benefit toward overall ipsilateral local control
when administered in addition to radiotherapy;
however, tamoxifen did appear to reduce the ipsilateral recurrence rate of DCIS (but not
invasive carcinoma) in the absence of radiotherapy.
Long term results of United Kingdom, Australia, and
New Zealand (UK/ANZ) DCIS trial*
enrolled 1,067 patients from 1987 to 1999, with 1,046 of these patients followed for a mean
of 8 years.
Patients randomized between lumpectomy f/b RT & lumpectomy only
Following a sector resection, microscopic clear resection was not required, and 50 Gy in
25 fractions to the whole breast was delivered in the majority of patients.
A split course, 54 Gy in 2-Gy fractions, delivered in two treatment series separated by a 2
week break was allowed.
No boost dose was delivered.
The in-breast failure risk reduction reported as 16% at 10 years (95% confidence
interval [CI] 10.3% to 21.6%) with a relative risk of 0.40 (95% CI 0.30 to 0.54).
Detailed analysis did not identify any patient or tumor characteristic subgroups that did
not benefit of postoperative radiotherapy.
Holmberg L, Garmo H, Granstrand B, et al. Absolute risk reductions for local recurrence after postoperative
radiotherapy after sector resection for ductal carcinoma in situ of the breast J Clin Oncol 2008;26:1247–125
SweDCIS trial (JCO2008)
Four randomized trials of BCS ±RT
(EORTC 2006; NSABP 1998; SweDCIS 2008; UKCCCR 2003).
Analysis confirmed a statistically significant benefit from the
addition of radiotherapy
on all ipsilateral breast events (hazards ratio (HR) 0.49; 95% CI
0.41 to 0.59, P < 0.00001)
ipsilateral DCIS recurrence (HR 0.64; 95% CI 0.41 to 1.01, P =
All the subgroups analysed benefited from addition of RT
No significant long-term toxicity from radiotherapy was found.
(Goodwin et al. 2009).
Early Breast Cancer Trialists’ Collaborative Group, Correa C, McGale P, Taylor C, et al. Overview of the randomized
trials of radiotherapy in dictal carcinoma in situ of the breast. J Natl Cancer Inst Mongr 2010;(41):162–167.
meta-analysis of the four randomized trials
total of 3,729 women eligible for analysis
RT reduced the absolute 10-year risk of any ipsilateral breast event (recurrent
DCIS or invasive disease) by 15.2% (standard error [SE] 1.6%, 12.9% vs.
28.1%, 2 p <.00001).
approximately reduces the risk of IBTR by 50%.
Subgroup analyses demonstrated that the absolute benefits of radiotherapy are
greater in women at increased risk for tumor recurrence, such as with
involved surgical margins. younger women, tumors that have high-grade or
little impact of RT on contralateral or distant events
RT IN DCIS
• Indication: after breast-conserving surgery
• Not Indicated :for post mastectomy & nodal irradiation
• Benefit of addition of RT to BCS more in
High grade & comedonecrosis
• Fields: tangential fields to the whole breast
• Dose: 45 to 50 Gy delivered in daily fractions of 180 to
• Radiation Boost :to the tumor bed may be added particularly
for close surgical margins, although the benefit of a boost
Van nuys prognostic index
• scoring system using histopathologic features in an attempt
to stratify patients according to local failure risk after
excision plus or minus whole-breast irradiation.
• There are 3 variables. Each variable is assigned a score of 1
to 3, and the sum total defined the Van Nuys Prognostic
• This scheme is drawn from the retrospective analysis of a
patient cohort in which there exist several methodologic
shortcomings, and it has not been independently
333 patients with pure DCIS treated with breast preservation were studied with
detection of local recurrence as the end point.
195 treated by excision only and 138 by excision plus radiation therapy
Score # 1 # 2 # 3
Path Other Comedo High Grade
Size <15mm 16-40mm >40mm
Margins >10mm 1-9mm < 1mm
Score 3 – 4 : Lumpectomy alone (local control is 100% vs 97%)
Score 5 – 7: Lumpectomy + Radiation (local control from 68%- 85%)
Score 8-9: Mastectomy
Cancer 1996 Jun 1;77(11):2267-74
no statistical difference in 8 year LRFS in patients with VNPI scores of 3 or 4,
regardless of whether or not radiation therapy was used (100% vs. 97%; P =
Patients with VNPI scores of 5, 6, or 7 received a statistically significant 17%
LRFS benefit when treated with radiation therapy (85% vs. 68%; P = 0.017).
Patients with scores of 8 or 9, showed the greatest relative benefit from
radiation therapy, however had recurrence rates in excess of 60% at 8
years regardless of irradiation, and should be considered for mastectomy.
Modified VNPI (Silverstein 2003).
• Retrospective review of 706 patients status post-BCT with or without RT
• scored based on four parameters:
1. tumor size (≤1.5, 1.6–4.0, >4.1 cm)
2. Pathology (non high-grade without necrosis, nonhigh-grade with
necrosis, high grade)
3. margins (≥1, 0.1–0.9, <0.1 cm)
4. age (>60, 40–60, <40 years)
For low-risk (score 4, 5, 6), no significant difference in 12-year local RFS
(>90–95%) with or without RT.
For intermediate-risk (score 7, 8, 9), addition of RT provided 12–15% 12-
year local RFS benefit.
For high-risk (score 10, 11, 12), mastectomy recommended due to high 5-
year LR (~50%) with or without RT.
Updated Van Nuys Prognostic Index
Parameter 1 Point 2 Points 3 Points
Size <15mm 16-40mm >40mm
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.)
LIMITATIONS OF VNPI INDEX
• Attempts to validate the VNPI scoring system have yielded mixed results
in various retrospective studies
MacAusland et al. 2007;
Di Saverio et al. 2008;
Gilleard et al. 2008
Altintas et al. 2011;
Lee et al. 2013;).
• Such studies have had uneven population distributions, most patients
having low to intermediate scores.
• Although patient age, tumor size, and tumor grade were set at patient
diagnosis, margin width may be downgraded by re-excision or TM.
• Such efforts to salvage treatment have resulted in a disproportionately
low rate of patients with high VNPI scores
A New Test for Estimating Recurrence Risk After
Lumpectomy with No Radiation
analyzes the activity of 21 genes that can influence how likely a
cancer is to grow and respond to treatment.
Oncotype DX test is both a prognostic test and predictive test
Oncotype DX test results assign a Recurrence Score — a number
between 0 and 100
recurrence Score Any Recurrence Invasive Recurrence
Low Risk less than 18 12% 5%
Intermediate Risk:18-31 25% 9%
High Risk: more than 31 27% 19%
Subset of patients in which RT can be avoided
• Van Nuys Prognostic Index :4-6
• DCIS size < 1.5 cm
• Negative margin > 1 cm
• Not high grade
• No comedo necrosis
• Age > 61
• ER + tumors
To date, prospective data have failed to validate the elimination of RT for
women completing BCS for DCIS
Few prospective trials have attempted to identify a subset of patients with
low-risk DCIS who may not benefit from the addition of radiation therapy
following a local excision
Confirmatory results are yet not available because either the trials stopped
early due to poor accrual or high LR or their results are awaited
The use of tamoxifen in the treatment of DCIS treated with BCS & RT is
unclear due to conflicting results.
The NSABP B-24 updated results showed that with a median follow-up of 163
months, the addition of tamoxifen translated into a significant 32% reduction in
invasive IBTR (9.0% vs. 6.6%, p = .025), a nonsignificant 16% reduction in
DCIS-IBTR (7.6% vs. 6.7%, p = .33), and a significant 32% reduction in
contralateral breast cancer (8.1% vs. 4.9%, p = .023); however, no survival
benefit was found
In contrast to the findings of the NSABP B-24 trial, the UK/ANZ DCIS trial
found that tamoxifen had no effect in reducing local recurrence rate when
combined with whole-breast radiation therapy
Because DCIS is a precursor to invasive breast cancer, tamoxifen is used as
target for preventive measures
Additional studies are being conducted evaluating the role of aromatase
inhibitors and Her2Neu targeted treatment in DCIS
• CBE & baseline mammogram 6 to 12 months after initial
therapy and at least annually thereafter
• Ipsilateral tumor recurrences usually detected on surveillance
mammography, although one-quarter may be detected on the
basis of changes on physical examination of the breast or
• Distant breast cancer metastases in the absence of regional
recurrence are unusual.
Management of Recurrence
• Local recurrences
• After excision only: local excision & RT
• After BCT+RT: treated with mastectomy.
• The clinical outcome of ipsilateral tumor recurrence is
governed by the nature of the recurrence.
• Patients with recurrent DCIS have an excellent prognosis,
with <1% risk of further recurrence after salvage mastectomy.
• Patients with invasive recurrence after breast-conserving
surgery for DCIS have a prognosis similar to those with early-
stage breast cancer, with a 15% to 20% risk of metastatic
recurrence at 8 years.