Use of radiation after Breast Conserving Surgery (BCS) for DCIS and early invasive breast cancer at Charleston Area Medical Center (CAMC): a study of compliance with National Comprehensive Cancer Network (NCCN) Guidelines.
Abstract: The National Comprehensive Cancer Network (NCCN) recommends that patients with ductal carcinoma in situ (DCIS) and stage I/II invasive breast cancer receive radiation therapy following breast conserving surgery (BCS). The purpose for our study was to determine 1) the percentage of patients with DCIS and stage I/II breast cancer who received radiation therapy following BCS and 2) the clinical factors associated with the use of radiation.

We retrospectively studied 606 patients treated between 2000 and 2007 with BCS for DCIS (n=104) and stage I/II breast cancer (n=502). Overall 93 percent of patients in our study received radiation therapy. We found that almost 85 percent and 95 percent of patients with DCIS and stage I/II breast cancer respectively received radiation therapy. Patients with invasive breast cancer who were less than 70 years of age and who received adjuvant systemic therapy were significantly more likely to receive radiation.

The data from our study indicate that the use of radiation following BCS is high at our institution. Periodic review of treatment practices at local hospitals is valuable in assessing compliance with national guidelines and in improving quality of care.
Subject: Breast cancer (Care and treatment)
Breast cancer (Prevention)
Lumpectomy (Health aspects)
Lumpectomy (Patient outcomes)
Radiotherapy (Health aspects)
Radiotherapy (Patient outcomes)
Authors: Dean, Chad T.
Jubelirer, Steven J.
Plants, Brian A.
Welch, Christine A.
Pub Date: 10/01/2009
Publication: Name: West Virginia Medical Journal Publisher: West Virginia State Medical Association Audience: Academic Format: Magazine/Journal Subject: Health Copyright: COPYRIGHT 2009 West Virginia State Medical Association ISSN: 0043-3284
Issue: Date: Oct, 2009 Source Volume: 105 Source Issue: S1
Geographic: Geographic Scope: United States Geographic Code: 1USA United States
Accession Number: 218949138
Full Text: Objectives

1. Determine NCCN guidelines for management of early stage invasive breast cancer in those undergoing lumpectomy.

2. Determine factors associated with use of radiation therapy.

3. Discuss limitation of this and other studies

Introduction

Multiple randomized trials have reported long-term results that demonstrate equivalent tumor control outcomes with breast conserving surgery (BCS) followed by radiation therapy as with modified radical mastectomy.(1-4) Fisher et al (1) reported a 20-year update of the NSABP (National Surgical Adjuvant Breast and Bowel Project) study B-06, a randomized trial comparing mastectomy, BCS without radiation, and BCS with radiation. The cumulative incidence of recurrent tumor in the ipsilateral breast was 14.3 percent in women who underwent BCS and breast irradiation as compared with 39.2 percent in women who underwent BCS without irradiation (P< 0.001). The hazard ratio for death among the women who underwent BCS followed by breast irradiation, as compared to those who underwent total mastectomy, was 0.97 (95% CI, 0.83 to 1.14, p = 0.74). Hammer et al (5) from the Cleveland Clinic reported similar recurrence rates (i.e. 10-15%) following both BCS/ radiation and mastectomy.

The National Comprehensive Cancer Network (NCCN) is a nonprofit alliance of the major federally funded comprehensive cancer centers. The NCCN has produced comprehensive guidelines for the care of 97% of all cancers seen by physicians. These guidelines are updated continually by disease-specific expert panels. The NCCN breast cancer guidelines recommend that radiation be used as a component of BCS for all patients with invasive breast cancer. (6) The guidelines allow for the use of BCS (pathologically negative margin required) plus hormone therapy (Tamoxifen or aromatase inhibitor) without breast irradiation in women age 70 or older with clinically negative lymph nodes and ER positive breast cancer. (6) The guidelines also recommend radiation after BCS for all patients with DCIS except those with low-grade lesions and tumors less than 0.5 cm. In such patients, radiation is considered optional. (6)

The purpose of our study was to determine 1) the percentage of patients with DCIS and stage I/II breast cancer who received radiation therapy after BCS in concordance with the NCCN guidelines and 2) patient and clinical factors that might influence the recommendations of radiation therapy in those who are eligible.

Methods

The CAMC Institutional Review Board (IRB) approved this study. The patients for this retrospective study were identified through the CAMC cancer registry. Inclusion criteria included any female with either DCIS or stage I/II invasive breast cancer (America Joint Committee on Cancer, sixth edition) that chose BCS during the years 2000 to 2007. Women who underwent a mastectomy following BCS due to positive margins, had bilateral breast cancer, presented for a second opinion only, and received no primary therapy at CAMC were excluded. Patients for whom BCS was contraindicated were excluded. This includes patients who 1) had received previous moderate or high dose radiation to the breast or chest wall; 2) were pregnant and would require radiation during pregnancy, 3) had diffuse suspicious or malignant appearing microcalcifications on mammography, 4) had widespread disease that cannot be incorporated by local excision through a single incision with a satisfactory cosmetic result; and 5) have positive pathologic margins despite attempts at re-excision.

Data were collected from the tumor registry and patients' medical records and included the following: age; race; insurance status; employment status; presence or absence of a radiation therapy facility in county of residence; tumor size; surgical margins; treatment (surgery, radiation, adjuvant therapy such as chemotherapy/hormones); estrogen receptor status; HER2/ neu status; radiation completion status; and reason for no treatment. Statistical analyses were performed using SAS. Results were considered statistically significant if p < 0.05.

Results

Data analysis was performed on 606 eligible patients. Of these, 104 (17.2%) were diagnosed with DCIS and the remaining 502 (82.8%) with stage I/II invasive breast cancer. Overall 93% of the patients received radiation therapy. Among patients with invasive breast cancer, 95% received radiation; in contrast only 85% of patients with DCIS received radiation therapy (p = 0.0003).

Table 1 and Table 2 show demographic and clinical factors that were observed for DCIS and stage I/II patients respectively. The mean age of patients was 58.5 [+ or -] 11.7 and 60.2 [+ or -] 12.3 for DCIS and stage I/II, respectively. When partitioned into age groups, the majority of patients in the DCIS and stage I/II groups were in the 50-69 age range. The majority of all patients were Caucasian, had some form of insurance, were employed, had a radiation therapy facility in the county in which they resided, had negative margins (DCIS = 96%; stage I/II = 96%) and had estrogen receptor positive tumors (DCIS = 68.5%; stage I/II = 78.6%). The majority of DCIS patients had tumors less than 1 cm (58.7%) and did not receive adjuvant hormone therapy (64.4%). Among the stage I/II patients, 74% had a tumor > 1 cm, 65.3% had a negative HER2/neu status, and 65.7% received adjuvant systemic therapy.

The proportion of DCIS patients receiving radiation therapy according to patient, tumor and treatment factors is listed in Table 1. On univariate analysis, there was no significant factor associated with the use of radiation therapy.

Among patients with stage I/II disease two factors were significantly associated with use of radiation on univariate analyses (Table 2): age and compliance with adjuvant systemic therapy. Almost all patients (98.2%) under age 50 received radiation therapy; in contrast, 88.6% of patients older than 70 received radiation therapy. In addition, those patients who received adjuvant hormone and/or chemotherapy were more likely to receive radiation compared to those who did not (97.6% vs. 89.0%, p < 0.0001).

The reasons for patients not receiving radiation therapy are shown in Table 3. For patients with DCIS, the most common reasons for not receiving radiation therapy were lost to follow up and physician decision. For patients with stage I/II, the most common reasons for not receiving radiation therapy were patient refusal and patient comorbidities.

Discussion

Using the results of the study by Buchholz et al. (7) as a benchmark, our data indicate that compliance to the NCCN guidelines is quite high. In our study, 85% and 95% of patients with DCIS and stage I/II breast cancer received radiation following BCS, respectively. In the study of Buchholz et al. (7), 82% and 94% of DCIS and stage I/II patients received radiation, respectively. However, lower rates of post BCS radiation have been reported by others. Bland et al. (8) reported radiation for DCIS and Stage I/II disease to be as low as 45% and 72%, respectively. However, it is important to note that Bland et al. studied patients from 1985 to 1995. More recently, Baxter et al (9) reported that only 54% of DCIS patients received radiation treatment after BCS (Table 4).

Several clinical and patient factors were predictors of radiation therapy use in our study. Patients over the age of 70 years with stage I/II breast cancer were less likely to receive radiation therapy after BCS than those younger. The NCCN treatment guidelines (6) state that radiation therapy for patients [greater than or equal to] 70 years with DCIS or invasive breast cancer is not mandatory if they have negative margins, small tumor size, estrogen receptor positive disease, no involved lymph nodes, and low grade tumor. We found no significance with regard to the use of radiation in this patient subset. We found that those patients who did not receive adjuvant hormones and/or chemotherapy were less likely to receive radiation therapy. This finding has been reported by others (7) and may represent a patient's overall noncompliance with medical direction.

[ILLUSTRATION OMITTED]

Limitations of this study include its retrospective design, thereby restricting us to the use of the data at hand and limiting interpretations of our findings. A second limitation is the relatively small sample size which may not be enough to identify other factors associated with radiation use. A third limitation is that some clinical information remained missing even after a review of data from the CAMC cancer registry and the patient's medical record. Radiation therapy is an outpatient procedure and may be underreported by the cancer registry. The cancer registry is charged with documenting the occurrence and incidence of cancer and not necessarily with documenting treatment and this has been reported by others (14,15). As an example, the initial review of patient information about post BCS radiation from the CAMC cancer registry between 20002007 indicated that only 45% of stage I/II breast cancer patients received radiation. After the medical records were reviewed, the percentage of patients receiving post-BCS radiation increased to 95%. The above discrepancy underscores the need for more accurate record keeping and reporting of information (especially treatment) to the cancer registry.

In conclusion, we found that the use of radiation following BCS in patients with DCIS and early invasive breast cancer is high. Periodic review of treatment practices at community hospitals, such as ours, is valuable in assessing compliance with national guidelines, such as the NCCN, and improving quality of care.

Acknowledgements: The authors would like to thank Ebenetta M. Rhinehart and Kathi J. McCormick from the CAMC tumor registry and Sharon Ross from the Charleston Radiation Therapy Consultants, for their assistance with this study.

References

(1.) Fisher B, Anderson S, Bryant J, Margolese RG, Deutsch M, Fisher ER, Jeong JH, Wolmark N. Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Eng J Med. 2002;347: 1233-1241.

(2.) Veronesi U, Cascinelli N, Mariani L, Greco M, Saccozzi R, Luini A, Aguilar M, Marubini E. Twenty-year follow-up of a randomized study comparing breast-conserving surgery with radical mastectomy for early breast cancer. N Engl J Med. 2002;347(16):1227-1232.

(3.) Poggi MM, Danforth DN, Sciuto LC, Smith SL, Steinberg SM, Liewehr DJ, Menard C, Lippman ME, Lichter AS, Altemus RM. Eighteen-year results in the treatment of early breast carcinoma with mastectomy versus breast conservation therapy; the National Cancer Institute Randomized Trial. Cancer. 2003 Aug 15;98:697-702.

(4.) EORTC Breast Cancer Cooperative Group; EORTC Radiotherapy Group, Bijker N, Meijnen P, Peterse JL, Bogaerts J, Van Hoorebeeck I, Julien JP, Gennaro M, Rouanet P, Avril A, Fentiman IS, Bartelink H, Rutgers EJ. Breast-conserving treatment with or without radiotherapy in ductal carcinoma-in-situ: ten-year results of European Organisation for Research and Treatment of Cancer randomized phase III trial 10853--a study by the EORTC Breast Cancer Cooperative Group and EORTC Radiotherapy Group. J Clin Oncol. 2006;24:3381-7.

(5.) Hammer C, Fanning A, Crowe J. Overview of breast cancer staging and surgical treatment options. Cleve Clin J Med. 2008;75:10-16.

(6.) Carlson RW, Allred DC, Anderson BO, Burstein HJ, Carter WB, Edge SB et al. NCCN Clinical Practice Guidelines in Oncology. National Comprehensive Cancer Network. 2009:V:1.

(7.) Buchholz TA, Theriault RL, Niland JC, Hughs ME, Ottesen R, Edge SB, et al. The use of radiation as a component of breast conservation therapy in National Comprehensive Cancer Network Centers. J Clin Oncol 2006; 24:361-369.

(8.) Bland KI, Menck HR, Scott-Conner CE, Morrow M, Winchester DJ, Winchester DP. The National Cancer Data Base 10-year survey of breast carcinoma treatment at hospitals in the United States. Cancer 1998;83:1262-1273.

(9.) Baxter NN, Virnig BA, Durham SB, Tuttle TM. Trends in the treatment of ductal carcinoma in situ of the breast. J Natl Cancer Inst. 2004;96:443-448.

(10.) Winchester DP. Menck HR, Osteen RT, Kraybill W. Treatment trends for ductal carcinoma in situ of the breast. Ann Surg Oncol. 1995;2:207-213.

(11.) Gold HT, Dick AW. Variation in treatment for ductal carcinoma in situ in elderly women. Med Care. 2004;42:267-275.

(12.) Nattinger AB, Hoffmann RG, Kneusel RT, Schapira MM. Relation between appropriateness of primary therapy for early-stage breast carcinoma and increased use of breast-conserving surgery. Lancet. 2000;356:1148-1153.

(13.) White J, Morrow M, Moughan J, Owen J, Pajak T, DesHarnais S, et al. Compliance with breast-conservation standards for patients with early-stage breast carcinoma. Cancer. 2003;97:893-904.

(14.) Malin JL, Kahn KL, Adams J, Kwan L, Laouri M, Ganz. Validity of cancer registry data for measuring the quality of breast cancer care. J Nat Cancer Inst. 2002;94:835-844.

(15.) Bickell NA, Chassin MR. Determining the quality of breast cancer care. Do tumor registries measure up? Ann Intern Med 2000;132:705-710.

CME Post-Test

17. The NCCN (National Comprehensive Cancer Network) breast cancer guidelines allow for the use of BCS (breast conserving surgery) plus hormone therapy without breast irradiation only in women who...

a. are age 70 or older

b. have clinically negative lymph nodes

c. are estrogen-receptor (ER) positive

d. have all of the above

18. All of the following are contraindications to breast conserving surgery (BCS) in patients with stage I/II breast cancer except...

a. prior moderate/high dose radiation to the breast or chest wall

b. diffuse malignant appearing microcalcifications on mammography

c. positive pathologic margins despite attempts at re-excision

d. tumor size [greater than or equal to] 3 centimeters

19. Among patients with stage I/II breast cancer in the present study, none of the following factors was associated with the use of radiation except.

a. Employment status

b. ER status

c. Insurance status

d. Age

e. Presence of radiation therapy facility in the county of residence

20. In the present study, factors significantly associated with the use of radiation therapy after BCS in those with DCIS include.

a. Age

b. Tumor size (< 1 cm vs. [greater than or equal to] 1 cm)

c. Insurance status

d. Estrogen receptor status

e. None of the above

Chad T. Dean [1] Steven J. Jubelirer, MD [2] Brian A. Plants, MD [3] Christine A. Welch, MS [1]

[1] CAMC, Outcomes Research, Charleston, WV

[2] CAMC, David Lee Cancer Center, Charleston, WV

[3] Charleston Radiation Therapy Consultants, Charleston, WV
Table 1. Clinical and patient factors affecting radiation therapy
completion in DCIS patients.

         Category                      Variable

Age                            <50
                               50-69
                               [greater than or equal to]70

Race                           White
                               All Others

Insurance Status               Insurance NOS
                               Medicare/Medicaid
                               Self-Pay
                               Unknown

Employment Status              Employed
                               Unemployed or Unknown

Radiation Facility in County   Yes
of Residence                   No

Tumor Size                     <1cm
                               [greater than or equal to]1cm

Surgical Margins               Positive/close
                               Negative

Received Hormone and/
or Chemo Therapy               Yes
                               No

HER2/neu                       Negative
                               Positive
                               Not Done
                               Unknown

ER Status                      Negative
                               Positive
                                                % Who
                                              Completed
                                  Total       Radiation
                                Population     Therapy

         Category               N      %       N    %    p-value

Age                            22    21.15   19   86.36    0.87
                               62    59.62   53   85.48
                               20    19.23   16   80.00

Race                           97    93.27   82   84.54    1.00
                               7     6.73    6    85.71

Insurance Status               71    68.27   63   88.73    1.00
                               25    24.04   22   88.00
                               1     0.96    1    100
                               7     6.73

Employment Status              67    64.42   58   86.57    0.46
                               37    35.58   30   81.08

Radiation Facility in County   76    73.08   62   81.58    0.22
of Residence                   28    26.92   26   92.86

Tumor Size                     44    58.67   39   88.64    0.39
                               31    41.33   30   96.77

Surgical Margins               4     3.85    4    100.00   1.0
                               100   96.15   84   84.00

Received Hormone and/
or Chemo Therapy               37    35.58   32   86.49    0.69
                               67    64.42   56   83.58

HER2/neu                       18    17.31   17   94.44    1.00
                               3     2.88    3    100.00
                               18    17.31
                               65    62.5

ER Status                      17    31.48   17   100.00   0.17
                               37    68.52   32   86.49

Table 2. Clinical and patient factors affecting radiation therapy
completion in stage I and II patients.

      Category                    Variable

Age                     <50
                        50-69
                        [greater than or equal to]70

Race                    White
                        All Others

Insurance Status        Insurance NOS
                        Medicare/Medicaid
                        Self-Pay
                        Unknown

Employment Status       Employed
                        Unemployed or Unknown

Radiation Facility in   Yes
County of Residence     No

Tumor Size              <1cm
                        [greater than or equal to]1cm

Surgical Margins        Positive/close
                        Negative

Received Hormone        Yes
and/or Chemo Therapy    No

HER2/neu                Negative
                        Positive
                        Borderline
                        Not Done
                        Unknown

ER Status               Negative
                        Positive

                                         % Who
                                       Completed
                           Total       Radiation
                        Population      Therapy

      Category           N      %      N      %      p-value

Age                     108   21.51   106   98.15    0.002
                        271   53.98   260   95.94
                        123   24.50   109   88.62

Race                    473   94.22   448   94.71    0.66
                        29    5.78    27    93.10

Insurance Status        305   60.76   295   96.72    0.19
                        176   35.06   164   93.18
                        8     1.59    8     100.00
                        13    2.59

Employment Status       289   57.57   276   95.58    0.31
                        213   42.43   199   93.43

Radiation Facility in   319   63.55   298   93.42
County of Residence     183   36.45   177   96.72    0.11

Tumor Size              123   26.00   118   95.93    0.92
                        350   74.00   335   95.71

Surgical Margins        20    3.98    20    100.00   0.62
                        482   96.02   455   94.40

Received Hormone        330   65.74   322   97.58    < 0.0001
and/or Chemo Therapy    172   34.26   153   88.95

HER2/neu                328   65.34   312   95.12    0.27
                        44    8.76    43    97.73
                        19    3.78
                        13    2.59
                        98    19.52

ER Status               96    21.43   89    92.71    .065
                        352   78.57   341   96.88

Table 3. Reasons noted for patients who did not receive radiation
therapy stage.

Reasons Given for Patients Not Receiving Radiation   DCIS   Stage I/II
Therapy

Lost to follow-up (No mention of radiation therapy     10         5
in chart)

Patient Refused--(No reason specified, worried
about side effects, or never showed up for              1        14
appointment)

Co-morbidities (scleroderma, Alzheimer's, post-op       1         5
stroke, developed other cancer, age > 90)

Physician reason (negative wide margins, low grade      4         3
tumor, patient referred to medical oncologist for
treatment)

Total                                                  16        27

Table 4. A Comparison of studies of patients with DCIS and Stage
I/II breast cancer who completed radiation therapy following breast
conservation surgery.

                                      DCIS
                                     % who      Stage I/II breast
                                   Completed      cancer (% who
       Study             Years        XRT)       completed XRT)

Buchholz (7)           1997-2002       82              94
Bland (8)              1985-1995       45              72
Baxter (9)             1992            45
                       1999            54
                       1985            38
Winchester (10)        1993            54
Baxter (9)             1992            45
                       1999            54
Gold (11)              1991-1996       39
Nattinger (12)         1983-1995                       75
White (13)             1994                            86
Dean (present study)   2000-2007       85              95
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