Non-Invasive Breast Cancer:Non-Invasive Breast Cancer:

Ductal Carcinoma In-situ

Vassi Gardikas, MD, FACSEllen Malek, CTR

2011 Oncology ServicesAnnual Report

Saint Agnes Medical CenterCancer Registry

1303 East Herndon AvenueFresno, CA 93720

559 450-3570www.samc.com

®

Ductal carcinoma in situ (DCIS, also known as intraductal carcinoma) is Ductal carcinoma in situ (DCIS, also known as intraductal carcinoma) is the most common type of non-invasive breast cancer or pre-cancer in the most common type of non-invasive breast cancer or pre-cancer in women. women. Ductal carcinomaDuctal carcinoma refers to the development of refers to the development of cancer cellscancer cells within the within the milk ductsmilk ducts of the breast. of the breast. In situIn situ means “in place” and refers means “in place” and refers to the fact that the cancer has not moved out of the duct and into any to the fact that the cancer has not moved out of the duct and into any surrounding tissue. surrounding tissue.

Ductal carcinoma in situ (DCIS) is non-invasive breast cancer that Ductal carcinoma in situ (DCIS) is non-invasive breast cancer that encompasses a wide spectrum of diseases ranging from encompasses a wide spectrum of diseases ranging from low gradelow grade lesions that are not life threatening to lesions that are not life threatening to high gradehigh grade lesions that may lesions that may harbor foci of invasive breast cancer. DCIS has been classified harbor foci of invasive breast cancer. DCIS has been classified according to architectural pattern (solid, cribriform, papillary, and according to architectural pattern (solid, cribriform, papillary, and micropapillary), tumor grade (high, intermediate, and low grade), and micropapillary), tumor grade (high, intermediate, and low grade), and the presence or absence of comedo histology.the presence or absence of comedo histology.

DCIS is a DCIS is a Stage 0Stage 0 cancer, the earliest form of breast cancer. Stage 0 cancer, the earliest form of breast cancer. Stage 0 breast cancer is a contained cancer that has not spread beyond the breast cancer is a contained cancer that has not spread beyond the ductal system (to the lymph nodes or other areas of the body). With ductal system (to the lymph nodes or other areas of the body). With proper treatment, the chances of surviving DCIS are very high. proper treatment, the chances of surviving DCIS are very high.

Introduction Introduction (2)(2)

Resource: Wikipedia.org

Different NamesDifferent Names

Ductal carcinoma in-situDuctal carcinoma in-situ Intraductal carcinomaIntraductal carcinoma Non-invasiveNon-invasive Pre-cancerPre-cancer Stage 0 Stage 0

Resource: Wikipedia.org

IntroductionIntroduction Ductal Carcinoma In-Situ is a highly curable form of breast cancer. Treatment Ductal Carcinoma In-Situ is a highly curable form of breast cancer. Treatment

options include options include breast conserving surgery (partial mastectomy)breast conserving surgery (partial mastectomy) or or mastectomy mastectomy (removal of the whole breast)(removal of the whole breast). .

Breast conserving surgery encompasses excision of the diseased portion of the Breast conserving surgery encompasses excision of the diseased portion of the breast only breast only or excision followed by radiationor excision followed by radiation therapytherapy, which is added to kill any , which is added to kill any cancer cells that potentially remain following lumpectomy. cancer cells that potentially remain following lumpectomy.

Radiation therapy accompanying wide local excision of DCIS is known to reduce Radiation therapy accompanying wide local excision of DCIS is known to reduce local recurrence by 50 percent.local recurrence by 50 percent.

Patients with ductal carcinoma in-situ who are treated with mastectomy seldom Patients with ductal carcinoma in-situ who are treated with mastectomy seldom recur locally or with distant metastatic disease. recur locally or with distant metastatic disease.

2003 SEER comparison data indicated that nationally 35% underwent excision 2003 SEER comparison data indicated that nationally 35% underwent excision alone, 39% excision plus radiation and 26% were treated by mastectomy. alone, 39% excision plus radiation and 26% were treated by mastectomy.

Of the 794 cases of DCIS receiving treatment at SAMC between 1995-2010, a Of the 794 cases of DCIS receiving treatment at SAMC between 1995-2010, a significantly lower percentage of cases, 18.3% (146) were treated by excision alone. significantly lower percentage of cases, 18.3% (146) were treated by excision alone. Again by contrast to the 2003 SEER data, a higher percent, 51.8% (412) were Again by contrast to the 2003 SEER data, a higher percent, 51.8% (412) were treated with excision plus radiation therapy. A similar, 28.7% (228) underwent treated with excision plus radiation therapy. A similar, 28.7% (228) underwent mastectomy. mastectomy.

IntroductionIntroduction

A recent study from researchers at Hoag Memorial Hospital Presbyterian in A recent study from researchers at Hoag Memorial Hospital Presbyterian in Newport Beach Newport Beach (Melvin Silverstein, MD, et al)(Melvin Silverstein, MD, et al), studied the , studied the patterns of recurrence patterns of recurrence in DCIS patients treated with lumpectomyin DCIS patients treated with lumpectomy. They noted that while women treated . They noted that while women treated with radiation following breast conserving surgery had a significantly lower with radiation following breast conserving surgery had a significantly lower recurrence rate, radiated patients experienced more invasive recurrences and recurrence rate, radiated patients experienced more invasive recurrences and had a longer time from initial treatment to recurrence. had a longer time from initial treatment to recurrence. (4)(4)

An additional study published in the Annals of Surgical Oncology by some of the An additional study published in the Annals of Surgical Oncology by some of the same researchers analyzed the same researchers analyzed the risk of recurrence after mastectomy for DCIS using risk of recurrence after mastectomy for DCIS using the USC/Van Nuys Prognostic Index.the USC/Van Nuys Prognostic Index. (5)(5)

With the above studies in mind, this report further examines the experience for With the above studies in mind, this report further examines the experience for Saint Agnes Medical Center from 1995-2010 with data compiled by the SAMC Saint Agnes Medical Center from 1995-2010 with data compiled by the SAMC

Cancer Registry.Cancer Registry.

1995-2010 SAMC Ductal Carcinoma In-situ1995-2010 SAMC Ductal Carcinoma In-situN=794N=794

As mentioned, over the sixteen year period, As mentioned, over the sixteen year period, 794 analytic cases of ductal 794 analytic cases of ductal carcinoma in situ (DCIS)carcinoma in situ (DCIS) were diagnosed and/or treated at Saint Agnes were diagnosed and/or treated at Saint Agnes Medical Center. Medical Center. Cases of Paget’s disease and lobular carcinoma in-situ Cases of Paget’s disease and lobular carcinoma in-situ (LCIS) were excluded from the study unless specified.(LCIS) were excluded from the study unless specified.

Of these, Of these, 99.6% were female99.6% were female and 0.4% were male (3). Of the two men and 0.4% were male (3). Of the two men in the study, one had two separate primaries, with DCIS involving both in the study, one had two separate primaries, with DCIS involving both breasts. breasts.

Median age at diagnosis was Median age at diagnosis was 6161..

Racial/ethnic distribution demonstrated Racial/ethnic distribution demonstrated 83%83% Non-Hispanic WhiteNon-Hispanic White, , 10.5% Hispanic10.5% Hispanic, , 4.5% Asian4.5% Asian and and 2% African American2% African American..

Resource: SAMC Cancer Registry

1995-2010 SAMC Ductal Carcinoma1995-2010 SAMC Ductal Carcinoma In-situIn-situcont.cont.N=794N=794

1% received No surgery (7) or surgery was Unknown (1). 1% received No surgery (7) or surgery was Unknown (1). 70% (558) underwent Partial Mastectomy 70% (558) underwent Partial Mastectomy (excision of the primary tumor, (excision of the primary tumor,

lumpectomy, less than mastectomy).lumpectomy, less than mastectomy).

Of the 558 who underwent Partial Mastectomy, Of the 558 who underwent Partial Mastectomy, 26% (146) had excision alone26% (146) had excision alone and and 74% (412) were treated with excision plus radiation therapy 74% (412) were treated with excision plus radiation therapy (inclusive of (inclusive of 8 MammoSite brachytherapy).8 MammoSite brachytherapy).

29% (228) were treated with Mastectomy 29% (228) were treated with Mastectomy (simple, total or *modified radical).(simple, total or *modified radical).

Quality control review was performed to explain Quality control review was performed to explain *modified radical mastectomy*modified radical mastectomy for the treatment of for the treatment of DCIS.DCIS. Findings indicate that this was a result of coding practice at the time sentinel lymph node Findings indicate that this was a result of coding practice at the time sentinel lymph node biopsy was introduced (approximately 1999). Subsequently when this became standard of care, biopsy was introduced (approximately 1999). Subsequently when this became standard of care, coding rules were updated and, confirmed to be applied appropriately in accordance with data coding rules were updated and, confirmed to be applied appropriately in accordance with data standards set forth by the California Cancer Registry and Commission on Cancer.standards set forth by the California Cancer Registry and Commission on Cancer.

Resource: SAMC Cancer Registry

1995-2010 SAMC Ductal Carcinoma In-situ1995-2010 SAMC Ductal Carcinoma In-situType of Surgery by Tumor GradeType of Surgery by Tumor Grade N=794N=794

6.6% 6%

35.5%

26.5%

43.4%

52%

14.5% 15.5%

Low Intermediate High Not Determined

Partial Mastectomy

Resource: SAMC Cancer Registry

N=558 N=228

1995-2010 SAMC Ductal Carcinoma In-situ1995-2010 SAMC Ductal Carcinoma In-situRecurrence Type by SurgeryRecurrence Type by SurgeryN=794N=794

3%

1%

0.5%

2%

0.5% 0.5% 0.5% 0.5%

Excis AloneN=146

Excis + XRTN=412

MastectomyN=228

Local, Nos Local, In-Situ Local, Invasive Distant

4

Resource: SAMC Cancer Registry

2

10

2 2 1 1 1

N=1N=5N=15N=2

USC/Van Nuys Prognostic IndexUSC/Van Nuys Prognostic Index USC/Van Nuys Prognostic Index is an USC/Van Nuys Prognostic Index is an

algorithm based on DCIS size, nuclear algorithm based on DCIS size, nuclear grade, necrosis, margin width and grade, necrosis, margin width and patient age. A calculation of these patient age. A calculation of these factors is summed into a single number factors is summed into a single number which then places the case into one of which then places the case into one of the three primary treatment groups. the three primary treatment groups.

USC/VN PI score can be used to aid in USC/VN PI score can be used to aid in the decision making process when the decision making process when considering the patient’s wishes and the considering the patient’s wishes and the doctor’s assessment of the most doctor’s assessment of the most appropriate care based on the individual.appropriate care based on the individual.

For the purposes of our study USC/VN PI For the purposes of our study USC/VN PI score was retrospectively applied for score was retrospectively applied for each SAMC case of recurrence and each SAMC case of recurrence and included in the following graphs.included in the following graphs.

Although some scores were high, our Although some scores were high, our findings were not consistent due to the findings were not consistent due to the lack of detail collected in the earlier lack of detail collected in the earlier years of the study period.years of the study period.

1995-2010 SAMC Ductal Carcinoma In-situ1995-2010 SAMC Ductal Carcinoma In-situ ObservationsObservations

Of the 794 patients with ductal carcinoma in-situ treated at Saint Agnes during this Of the 794 patients with ductal carcinoma in-situ treated at Saint Agnes during this period there were period there were a total of 23 recurrences the majority of which were local (22) a total of 23 recurrences the majority of which were local (22) with one distant recurrencewith one distant recurrence. .

As expected the bulk of recurrences (20) were observed in those who underwent As expected the bulk of recurrences (20) were observed in those who underwent partial mastectomy (wide local excision, lumpectomy, less than total mastectomy). partial mastectomy (wide local excision, lumpectomy, less than total mastectomy).

Of those treated by excision alone (146) there were 6 (4%) recurrences. The Of those treated by excision alone (146) there were 6 (4%) recurrences. The average time to recurrence was less than 24 months. Two of the recurrences were average time to recurrence was less than 24 months. Two of the recurrences were invasive, observed at two and six years following initial treatment. invasive, observed at two and six years following initial treatment.

The excision plus radiation therapy (412) group noted 14 (3.4%) recurrences with The excision plus radiation therapy (412) group noted 14 (3.4%) recurrences with two being invasive. The average time to recurrence was four years. two being invasive. The average time to recurrence was four years.

For those who had a mastectomy there were 3 (1.3%) recurrences. Two had local For those who had a mastectomy there were 3 (1.3%) recurrences. Two had local recurrence, one being in-situ and the other invasive. The third case experienced recurrence, one being in-situ and the other invasive. The third case experienced uncommon distant recurrence. uncommon distant recurrence.

When compared to national data for the years 2000-2009 Saint Agnes Medical When compared to national data for the years 2000-2009 Saint Agnes Medical Center matched standard of care in the detection of breast cancer at its earliest Center matched standard of care in the detection of breast cancer at its earliest stage (Stage 0), treatment by all modalities and in the surgical treatment of ductal stage (Stage 0), treatment by all modalities and in the surgical treatment of ductal carcinoma in-situ.carcinoma in-situ.

1995-2010 SAMC Ductal Carcinoma In-situ1995-2010 SAMC Ductal Carcinoma In-situPartial Mastectomy by Pattern of Recurrence Partial Mastectomy by Pattern of Recurrence N=558N=558

# of # of PtsPts

SurgerySurgery XRTXRT Largest Tumor Largest Tumor Dimension Dimension *multifocal*multifocal

GradeGrade MarginsMargins VNPI VNPI ScoreScore

Recurrence Recurrence (Recurrence Unknown (Recurrence Unknown

excluded N=6)excluded N=6)

TypeType Year Year RecurredRecurred

11 PartialPartial NO 5.5 cm5.5 cm HighHigh NegativeNegative 88 LOCALLOCAL In-situIn-situ 10 mo10 mo

22 PartialPartial NO 0.25 cm0.25 cm IntermedIntermed NegativeNegative 66 LOCALLOCAL In-situIn-situ 8 mo8 mo

33 PartialPartial NO 1.2 cm1.2 cm UnkUnk NegativeNegative 55 LOCALLOCAL In-situIn-situ 13 mo13 mo

44 PartialPartial NO 1.4 cm1.4 cm LowLow NegativeNegative 44 LOCALLOCAL InvasiveInvasive 6 yrs6 yrs

55 PartialPartial NO 0.1 cm0.1 cm UnknownUnknown NegativeNegative 66 LOCALLOCAL InvasiveInvasive 2 yrs2 yrs

66 PartialPartial NO 1.8 cm1.8 cm HighHigh NegativeNegative 88 LOCALLOCAL In-situIn-situ 17 mo17 mo

77 PartialPartial Yes 2.0 cm2.0 cm HighHigh NegativeNegative 88 LOCALLOCAL In-situIn-situ 10 yrs10 yrs

88 PartialPartial Yes 2.5 cm2.5 cm HighHigh NegativeNegative 88 LOCALLOCAL In-situIn-situ 4 yrs4 yrs

99 PartialPartial Yes UnknownUnknown HighHigh CloseClose 88 LOCALLOCAL In-situIn-situ 9 yrs9 yrs

1010 PartialPartial Yes 1.5 cm1.5 cm HighHigh CloseClose 77 LOCALLOCAL NOSNOS 2.5 yrs2.5 yrs

1111 PartialPartial Yes UnknownUnknown HighHigh CloseClose 77 LOCALLOCAL In-situIn-situ 1 yr1 yr

1212 PartialPartial Yes **0.3 cm0.3 cm IntermedIntermed UnknownUnknown 66 LOCALLOCAL In-situIn-situ 5 yrs5 yrs

1313 PartialPartial Yes 0.5 cm0.5 cm HighHigh NegativeNegative 77 LOCALLOCAL InvasiveInvasive 3.5 yrs3.5 yrs

1414 PartialPartial Yes 1.1 cm1.1 cm HighHigh NegativeNegative 66 LOCALLOCAL In-situIn-situ 1 yr1 yr

1515 PartialPartial Yes 1.5 cm1.5 cm HighHigh NegativeNegative 77 LOCALLOCAL In-situIn-situ 1.5 yrs1.5 yrs

1616 PartialPartial Yes UnknownUnknown HighHigh NegativeNegative 88 LOCALLOCAL In-situIn-situ 2.5 yrs2.5 yrs

1717 PartialPartial Yes 2.5 cm2.5 cm HighHigh NegativeNegative 88 LOCALLOCAL InvasiveInvasive 4.5 yrs4.5 yrs

1818 PartialPartial Yes **1.0 cm1.0 cm IntermedIntermed NegativeNegative 66 LOCALLOCAL In-situIn-situ 2 yrs2 yrs

1919 PartialPartial Yes 2.2 cm2.2 cm HighHigh < 1 mm< 1 mm 99 LOCALLOCAL NOSNOS 4.5 yrs4.5 yrs

2020 PartialPartial Yes 8.5 cm8.5 cm IntermedIntermed NegativeNegative 99 LOCALLOCAL In-situIn-situ 4 yrs4 yrs

1995-2010 SAMC Ductal Carcinoma In-situ1995-2010 SAMC Ductal Carcinoma In-situ Recurrence Following MastectomyRecurrence Following Mastectomy N=228N=228

# of # of PtsPts SurgerySurgery XRTXRT

Largest Largest Tumor Tumor

Dimension Dimension *multifocal*multifocal

GradeGrade MarginsMargins VNPI VNPI ScoreScore

RecurrenceRecurrence(Recurrence (Recurrence

Unknown excluded Unknown excluded N=1)N=1)

TypeTypeYear Year RecurredRecurred

11 MASTMAST NO 2.0cm2.0cm HighHigh NEGNEG 88 LOCALLOCAL In-situIn-situ 2 yrs2 yrs

22 MASTMAST NO 9.0cm9.0cm HighHigh CLOSECLOSE 1111 LOCALLOCAL InvasiveInvasive 2.5 yrs2.5 yrs

33 MASTMAST NO *2.5cm*2.5cm HighHigh NEGNEG 77 DISTANTDISTANT CNSCNS 4 yrs4 yrs

Resource: SAMC Cancer Registry

Risk of Recurrence After Mastectomy for DCISRisk of Recurrence After Mastectomy for DCISComparison Melvin J. Silverstein, et al Comparison Melvin J. Silverstein, et al (5)(5)

MJSMJS SAMCSAMC

TOTAL TOTAL 14721472 794794

MASTMAST 496 496 34%34%

228 228 29%29%

RECURRECUR 11 11 2.2%2.2%

3 3 1.3%1.3%

In this prospective study by MJS In this prospective study by MJS group 1,472 patients were group 1,472 patients were observed. None received any form observed. None received any form of post mastectomy adjuvant of post mastectomy adjuvant treatment. Cited average length of treatment. Cited average length of follow up was 83 months. follow up was 83 months.

Mastectomy was selected as Mastectomy was selected as treatment of choice 5% more treatment of choice 5% more frequently by MJS group.frequently by MJS group.

SAMC patients with DCIS treated by SAMC patients with DCIS treated by mastectomy exhibited overall mastectomy exhibited overall similar risk of recurrence. similar risk of recurrence.

2000-2009 NCDB Benchmark Comparison 2000-2009 NCDB Benchmark Comparison Non-Invasive Breast Cancer Non-Invasive Breast Cancer (all histologies)(all histologies)

18.4%SAMC N=602

19%NCDB

N=355,964

Stage 0

2000-2009 NCDB Benchmark Comparison2000-2009 NCDB Benchmark ComparisonNon-Invasive Breast Cancer Non-Invasive Breast Cancer (all histologies)(all histologies)

First Course TreatmentFirst Course Treatment

0.2%2%

38%

45%

13%

9%

18%

22%

28%

18%

2.8%4%

None Surg Surg/H Surg/XRT Surg/XRT/H Other

SAMC NCDB

2000-2009 NCDB Benchmark Comparison2000-2009 NCDB Benchmark ComparisonNon-Invasive Breast Cancer Non-Invasive Breast Cancer (all histologies)(all histologies) First Course SurgeryFirst Course Surgery

0.5% 2.3%

69% 68%

24% 23.2%

6% 5.5%0.5% 1%

No Surg Partial Total Modified Mast,Nos/Other

SAMC

NCDB

RecommendationsRecommendations It is suggested by the findings of this report that the USC/Van Nuys Prognostic It is suggested by the findings of this report that the USC/Van Nuys Prognostic

Index may be a useful aid in the decision making process for those patients Index may be a useful aid in the decision making process for those patients diagnosed with DCIS. ‘diagnosed with DCIS. ‘With advancing technology, there will come a time when With advancing technology, there will come a time when patients with DCIS can be better defined as to whether or not their disease is likely patients with DCIS can be better defined as to whether or not their disease is likely to progress. Those patients will likely need treatment, whereas others can simply to progress. Those patients will likely need treatment, whereas others can simply be monitoredbe monitored.’ ~ Medscape Medical News, July 10, 2010, Roxanne Nelson..’ ~ Medscape Medical News, July 10, 2010, Roxanne Nelson.

American Cancer Society recommendations for early detection of breast cancer American Cancer Society recommendations for early detection of breast cancer include for women age 20 – 39 a clinical breast examination every 3 years, and include for women age 20 – 39 a clinical breast examination every 3 years, and annual mammography beginning at age 40. Optional recommendation was annual mammography beginning at age 40. Optional recommendation was starting at age 20, monthly breast self-examination.starting at age 20, monthly breast self-examination.

Saint Agnes reminds women to Never Keep A Lump Secret; Saint Agnes reminds women to Never Keep A Lump Secret; ‘Don’t keep it a secret. ‘Don’t keep it a secret. TELL YOUR DOCTOR IMMEDIATELY. Instead of a screening mammogram, you will TELL YOUR DOCTOR IMMEDIATELY. Instead of a screening mammogram, you will be scheduled for a diagnostic mammogram. This is the only type of mammogram be scheduled for a diagnostic mammogram. This is the only type of mammogram that provides the of detail necessary to adequately examine the area in question. that provides the of detail necessary to adequately examine the area in question. When you arrive for your appointment, TELL THE TECHNICIAN ABOUT THE LUMP When you arrive for your appointment, TELL THE TECHNICIAN ABOUT THE LUMP and where it’s located SO SHE CAN ALERT THE RADIOLOGIST.’ and where it’s located SO SHE CAN ALERT THE RADIOLOGIST.’

If you ever detect a lump in your breast, TELL YOUR DOCTOR RIGHT AWAY, and If you ever detect a lump in your breast, TELL YOUR DOCTOR RIGHT AWAY, and when you arrive for the mammogram BE SURE AND TELL THE TECHNICIAN. Some when you arrive for the mammogram BE SURE AND TELL THE TECHNICIAN. Some things deserve to be kept secret. A LUMP IS NEVER ONE OF THEM.things deserve to be kept secret. A LUMP IS NEVER ONE OF THEM.

ResourcesResources

(1)(1) SAMC Cancer Registry database;SAMC Cancer Registry database; www.samc.comwww.samc.com *Comment: This report is developed from our hospital based registry experience which is not*Comment: This report is developed from our hospital based registry experience which is not

‘ ‘population based’ datapopulation based’ data..

(2)(2) Ductal Carcinoma In-situ definition and anatomy; Ductal Carcinoma In-situ definition and anatomy; www.wwww.wikipedia.orgikipedia.org

(3)(3) National Cancer Data Base Benchmark Comparison Reports; National Cancer Data Base Benchmark Comparison Reports; www.facs.orgwww.facs.org

(4) ‘(4) ‘Difference in Recurrence Patterns by Treatment in Patients with DCISDifference in Recurrence Patterns by Treatment in Patients with DCIS’,’, Janie Wong Grumley MD, Melvin J. Silverstein MD, Michael D. Lagios MD,Janie Wong Grumley MD, Melvin J. Silverstein MD, Michael D. Lagios MD, Jessica Rayhanabad MD, Stephanie F. Valente DO. Jessica Rayhanabad MD, Stephanie F. Valente DO.

(5) ‘(5) ‘Analyzing Risk of Recurrence after Mastectomy for DCIS: A New Use forAnalyzing Risk of Recurrence after Mastectomy for DCIS: A New Use for USC/Van Nuys Prognostic IndexUSC/Van Nuys Prognostic Index’,’, Leah Kelley MD, Melvin J. Silverstein MD, Leah Kelley MD, Melvin J. Silverstein MD, Lisa Guerra MD.Lisa Guerra MD.