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Keywords:

  • breast cancer;
  • ductal carcinoma in situ;
  • radiation therapy;
  • decision analysis

Abstract

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. FUNDING SOURCES
  7. CONFLICT OF INTEREST DISCLOSURES
  8. REFERENCES

BACKGROUND:

The benefit of adding radiation therapy after excision of ductal carcinoma in situ (DCIS) is widely debated. Randomized clinical trials are underpowered to delineate long-term outcomes after radiation.

METHODS:

The authors of this report constructed a Markov decision model to simulate the clinical course of DCIS in a woman aged 60 years who received treatment with either of 2 breast-conserving strategies: excision alone or excision plus radiation therapy. Sensitivity analyses were used to study the influence of risk of local recurrence, likelihood of invasive disease at recurrence, surgical choice at recurrence, and patient age at diagnosis on treatment outcomes.

RESULTS:

The addition of radiation therapy was associated with slight improvements in invasive disease-free and overall survival. However, radiation therapy decreased the chance of having both breasts intact over a patient's lifetime. Radiation therapy improved survival by 2.1 months for women who were diagnosed with DCIS at age 60 years but decreased the chance of having both breasts by 8.6% relative to excision alone. The differences in outcomes between the treatment strategies became smaller with increasing age at diagnosis. Sensitivity analyses revealed a greater benefit for radiation with an increased likelihood of invasive recurrence. The decrement in breast preservation with radiation therapy was mitigated by an increased likelihood of mastectomy at the time of recurrence or new breast cancer diagnosis.

CONCLUSIONS:

The current analysis quantified the benefits of radiation after excision of DCIS but also revealed that radiation therapy may increase the likelihood of eventual mastectomy. Therefore, the authors concluded that patient age and preferences should be considered when making the decision to add or forgo radiation for DCIS. Cancer 2012;. © 2011 American Cancer Society.

With increasing adoption of mammography, the incidence of ductal carcinoma in situ (DCIS) has risen dramatically. DCIS currently represents up to 33% of the malignancies identified by mammograms1, 2 and >25% of new breast cancer diagnoses.3, 4 Although mastectomy was once the standard surgical procedure for the treatment of DCIS, the majority of newly diagnosed patients now undergo breast-conserving surgery.3

The need for radiation therapy after breast-conserving surgery for DCIS is widely debated. Randomized trials studying the effect of adding radiation therapy for DCIS have demonstrated a reduction in local recurrence with radiation.5-9 However, some analyses have demonstrated low rates of recurrence with omission of radiation therapy in carefully selected patients,10, 11 whereas others have demonstrated persistently high rates of local recurrence even among highly selected patients.12, 13

Differences in the perceived risk of recurrence without radiation therapy may contribute to the significant heterogeneity observed in the management of DCIS. Population-based analyses indicate that, among patients who undergo breast-conserving surgery for DCIS, approximately 50% do not receive radiation, and there is significant regional variation in its use.2, 14, 15 The prevalence of DCIS and the marked variability in its patterns of care may explain the placement of DCIS management among the highest priority topics in the Institute of Medicine's list of areas in need of comparative-effectiveness research.16

Radiation reduces the risk of local recurrence to approximately half of that without radiation therapy.5-9 When DCIS recurs, half of the recurrences still are DCIS, but the other half are invasive breast cancers.5-8 Despite a reduction in invasive cancer recurrence, randomized trials have failed to demonstrate any difference in survival between treatment arms.5-9 However, even in aggregate, these trials are underpowered to detect small differences in survival. In the invasive breast cancer setting, a meta-analysis of radiation after breast-conserving surgery did not indicate a survival advantage until 10 to 15 years after randomization.17 A survival benefit from radiation therapy for DCIS is likely to be even more difficult to detect, because the reduction in local recurrence with radiation is smaller than that for invasive disease, and only about half of recurrences represent invasive disease.

The decision about whether to add radiation therapy after excision for DCIS is not straightforward. Radiation generally is delivered to the whole breast and requires a commitment to daily treatments for 6 weeks. Although it is tolerated fairly well, radiation therapy exposes patients to potential transient side-effects, including fatigue and skin toxicity, and to a very slightly increased risk of secondary malignancies.17 It is noteworthy that the use of radiation usually commits a patient to mastectomy should a local recurrence or new cancer develop in the same breast. Full-dose radiation can be given only once to a single breast because the limits of normal tissue tolerance. Conversely, radiation therapy reduces the risk of local recurrence, including invasive local recurrence. Not all local recurrences are amenable to breast-conserving surgery even if the patient has not received previous radiation. Moreover, should a patient suffer an invasive local recurrence, then there is the potential for spread to the lymph nodes and/or distant metastases, which ultimately may compromise survival.

The decision about whether to add radiation to breast-conserving surgery for DCIS requires a weighing of its risks and benefits. To help clarify the nature of these tradeoffs, we developed a decision analysis to gain insights into the magnitude of benefits and disadvantages of adding radiation therapy after surgery for DCIS using available data to model the downstream implications of recurrence.

MATERIALS AND METHODS

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. FUNDING SOURCES
  7. CONFLICT OF INTEREST DISCLOSURES
  8. REFERENCES

Decision-Analytic Model

We constructed a Markov decision-analytic model (Fig. 1) to simulate the clinical history women aged 60 years after breast-conserving surgery for DCIS using TreeAge Pro 2008 (TreeAge Software, Williamstown, Mass). We separately examined outcomes for women diagnosed at ages 45 years and 75 years. This Markov model18 allows individuals to make transitions monthly between health states of being well, having recurrent local disease, having a new breast cancer, being well after the diagnosis of a recurrence or new breast cancer, having metastatic cancer, and dying. We created separate states to keep track of the number of previously irradiated and nonirradiated breasts. The model compared the amount of time in the states after treatment with excision alone versus excision plus radiation therapy and was run until all patients had died. The outcomes studied were invasive disease-free survival, life expectancy, and the probability of having both breasts intact over a lifetime (ie, not undergoing either unilateral or bilateral mastectomy). The impact of radiation therapy was determined by reducing the risk of local recurrence compared with management without radiation.

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Figure 1. This is a simplified diagram of the Markov decision-analysis model. The square on the left is a decision lymph node and represents the choice between excision alone and excision followed by radiation therapy. The brace signifies a subtree that occurs for all branches of the decision tree leading to that brace. A simulated patient enters the Markov process after each treatment choice in which, if the patient remains alive, the green circles are chance nodes that represent the various possible outcomes: remaining well without disease, having a local recurrence, having a new breast cancer, or dying from other causes. If a local recurrence or new breast cancer is diagnosed, then another chance node is encountered that represents treatment with mastectomy or breast-conserving therapy. Local recurrence or a new breast cancer changes the chances of dying from breast cancer. The Markov cycle represents a single month during which a health state may change. At the end of each branch is a terminal node that describes the health state in which patients will begin the next 1-month cycle. The asterisk indicates that the actual model has separate “alive” states to keep track of the number of intact breasts and the number of previously irradiated breasts. The probability estimates from the literature listed in Table 1 determine the likelihood of chance events. Although it is not indicated in this figure for simplicity, a women remains at risk of a new breast cancer for her entire lifetime even after receiving radiation therapy for a recurrence. DCIS indicates ductal carcinoma in situ.

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Model Assumptions

We assumed that risk of local recurrence was constant for 10 years and was zero thereafter and that the risk reduction with radiation therapy was constant over time. We did not include excess mortality from radiation therapy, because newer techniques of delivering radiation in the breast-conservation setting are unlikely to increase mortality.17 We also assumed that DCIS itself without local recurrence carries no risk of breast cancer mortality. We assumed that a patient who developed a local recurrence or a new primary cancer in a previously irradiated breast would undergo mastectomy, which is standard practice. Patients who had not received previous radiation could receive breast-conserving therapy (excision and radiation) with a probability dependent on the stage of the recurrent or new disease. We assumed that patients who were diagnosed simultaneously with metastatic disease and local recurrence or a new breast cancer would not undergo mastectomy. Once a patient was diagnosed with metastases, she remained in the metastatic disease health state until death.

All recurrences in the ipsilateral breast within 10 years of diagnosis were assumed to be local recurrences. After 10 years, the ipsilateral breast carried the same risk of new breast cancer as the contralateral breast. A simulated patient was at risk for developing a new breast cancer during her entire lifetime at a rate dependent on the number of breasts. At the time of local recurrence or a new breast cancer diagnosis, disease stage determined the risk of death from breast cancer over the next 10 years.

Data Sources

Table 1 presents the base-case data estimates and ranges used in sensitivity analyses.

Table 1. Model Parameters
VariableBaseline Value (Range Studied)Reference
  1. Abbreviations: LR, local recurrence; NCI, National Cancer Institute; RT, radiation therapy.

Risk of LR at 10 y without RT0.2495 (0.15-0.35)Bijker 20065
Proportion reduction in LR with RT0.46 (0.3-0.7)Bijker 20065
Proportion of invasive LR0.50 (0.3-0.7)Bijker 2006,5 Fisher 20016
Stage distribution of invasive LR NCI 201019
 Stage I0.61 
 Stage II0.27 
 Stage III0.07 
 Stage IV0.05 
Ten-year breast cancer-specific mortality Olivotto 200320
 Stage I0.08 
 Stage II0.27 
 Stage III0.52 
 Stage IV0.88 
Risk of contralateral breast cancer/y0.00812 (0.004-0.010)Fisher 199921
Proportion of invasive new breast cancer0.687 (0.3-0.8)Bijker 2006,5 Fisher 199921
Stage distribution of invasive new breast cancer NCI 201019
 Stage I0.63 
 Stage II0.29 
 Stage III0.05 
 Stage IV0.03 
Proportion of mastectomy by stage NCI 201019
 Stage 0, noninvasive0.25 
 Stage I0.28 
 Stage II0.49 
 Stage III0.73 
Likelihood of local recurrence with and without radiation therapy

The baseline rate of local recurrence and the effect of radiation on that rate were derived from the European Organization for Research and Treatment of Cancer Trial 10853, which randomized patients with DCIS to radiation therapy or no further treatment after excision.5 This study provides recent randomized data with 10-year follow-up; therefore, techniques of margin assessment and radiation may be more similar to those performed currently. In sensitivity analyses, we assessed the influence of varying the rate of local recurrence and used a range that included the higher rate observed in the National Surgical Adjuvant Bowel and Breast Project (NSABP) B-17 study.6 We assumed that the rate of local recurrence did not vary with age at diagnosis. The proportions of local recurrences and new contralateral breast cancers with invasive (as opposed to in situ) histology were derived from randomized data of patients with DCIS (Table 1).5, 6, 21

Treatment and outcomes after local recurrence

The probability of undergoing mastectomy versus breast-conserving surgery for a local recurrence or a new primary cancer in a breast that had not been previously irradiated was a function of the stage at which the new cancer was diagnosed and was derived from treatment patterns among newly diagnosed women in the Surveillance Epidemiology and End Results (SEER) limited-use database (1995-2005) (Table 1). The stage distribution of invasive local recurrence after DCIS was specified according to the stage distribution of invasive ipsilateral breast cancer diagnoses among women with a prior diagnosis of DCIS in the database.

Likelihood of and outcomes after new breast cancers in the contralateral breast

The stage distribution of invasive new breast cancers followed the distribution of invasive contralateral breast cancer diagnoses among women with prior DCIS in SEER. The baseline rate of developing a new breast cancer was determined by the rate of contralateral breast cancers reported in the no-tamoxifen arm of the NSABP B-24 study, which randomized women undergoing excision and radiation for DCIS to tamoxifen or placebo.21

Breast cancer and nonbreast cancer mortality

Stage-specific mortality rates associated with a new invasive breast cancer or local recurrence were taken from a population-based series of patients with newly diagnosed breast cancer treated in British Columbia from 1989 to 1997.20 The likelihood of dying from other causes as a function of age was derived from 2004 US life tables for women.22

Sensitivity Analyses

Variables with significant variation across data sources or those that may meaningfully influence model outcomes were tested with sensitivity analyses. These variables included local recurrence risk, reduction in recurrence with radiation, rate of developing new breast cancer, proportion of local recurrence or new cancer that is invasive, and likelihood of mastectomy upon recurrence or new cancer in a previously nonirradiated breast. These variables were tested over a wide range of values. We studied the effect of simultaneously varying the risk of local recurrence and likelihood of mastectomy upon recurrence or new cancer in a previously nonirradiated breast on lifetime breast preservation. We also examined the effect across age cohorts of simultaneously varying local recurrence risk and the proportion of local recurrence that is invasive disease on survival.

RESULTS

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. FUNDING SOURCES
  7. CONFLICT OF INTEREST DISCLOSURES
  8. REFERENCES

The model results indicate that adding radiation therapy to excision alone increases invasive disease-free survival and overall survival. On average, for women aged 60 years at diagnosis, radiation therapy increases invasive disease-free survival from 233.4 months to 245.1 months (a difference of 11.7 months) and increases overall survival from 277.9 months to 280.0 months (a difference of 2.1 months). Younger women experience greater benefits. For women aged 45 years, radiation increases invasive disease-free survival from 340.6 months to 359.1 months (a difference of 18.5 months) and increases overall survival from 426.8 months to 430.8 months (a difference of 4.0 months). For women aged 75 years, the benefit from radiation therapy is 5.5 months and 0.7 months for invasive disease-free survival and overall survival, respectively.

However, the addition of radiation therapy decreases the likelihood of having intact breasts or being without mastectomy during a patient's entire lifetime. For women who are diagnosed with DCIS at age 60 years, the chance of maintaining both breasts (ie, avoiding mastectomy) throughout their lifetime is 73.5% with radiation therapy and 82.1% with excision alone (a difference of 8.6%). For women who are diagnosed at age 45 years, this chance is 63.5% with radiation therapy and 74.8% with excision alone (a difference of 11.3%). For women who are diagnosed at age 75 years, the decrement in breast preservation with radiation is smaller at 5.3%.

Sensitivity analyses reveal that the model results are consistent over a wide range of values for key variables (Table 2). Survival benefits with radiation therapy increase with greater risk of local recurrence, greater reduction in local recurrence with radiation, and greater proportion of local recurrence and new cancer diagnoses that is invasive disease. The effect of radiation therapy on breast preservation diminishes if the effectiveness of radiation in preventing recurrence increases or the likelihood of undergoing mastectomy at the time of recurrence or a new cancer diagnosis in a previously nonirradiated breast increases compared with baseline estimates.

Table 2. One-Way Sensitivity Analyses for the Addition of Radiation Therapy in Women Aged 60 Years
VariableBaseline ΔRange StudiedInvasive DFS 11.7 moOS 2.1 moPercentage With Both Breasts During Lifetime −8.6%
   Δ of Range, moΔ of Range, moΔ of Range, %
  • Abbreviations: Delta (Δ), difference with the addition of radiation therapy; DFS, disease-free survival; LR, local recurrence; OS, overall survival; RT, radiation therapy.

  • a

    In baseline analysis, this variable is a function of the stage of recurrence or new diagnosis; on average, it is 0.32.

LR at 10 y0.24950.15-0.357.0-16.71.3-3.0−7.6 to −9.6
Reduction in LR with RT0.460.30-0.708.0-17.41.4-3.1−11.6 to −4.1
Proportion of invasive LR0.500.30-0.709.0-15.91.4-2.9−9 to −8.2
Proportion of invasive new cancer0.690.30-0.8011.2-11.92.1-2.2−9 to −8.5
Contralateral breast cancer/y0.0080.004-0.01012.1-11.62.1-2.2−10 to −8.1
Proportion mastectomy at recurrence or new cancer if no previous RT0.32a0.20-0.4811.7-11.52.1-2.1−11.7 to −4.3

Simultaneously varying the risk of local recurrence and the proportion of local recurrence that is invasive disease (Figs. 2, 3) demonstrates greater benefit from radiation therapy as the risk of invasive recurrence increases by increasing either the overall risk of recurrence or the likelihood that a recurrence is invasive. At the highest rates of invasive recurrence we examined, the survival benefit from radiation was 6 to 8 months for women aged 45 years, 3 to 4 months for women aged 60 years, and <2 months for women aged 75 years.

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Figure 2. This chart illustrates the overall survival benefit with radiation therapy according to age at diagnosis using baseline estimates and maximum and minimum benefit estimates. The benefit to survival with radiation therapy is plotted against age at diagnosis. The blue line represents the benefit using baseline assumptions (a 10-year risk of local recurrence without radiation therapy of 0.2495 and 50% of recurrences consisting of noninvasive disease), the pink line represents the maximum possible radiation benefit (a 10-year risk of local recurrence of 0.35 and 70% of recurrences consisting of invasive disease), and the green line represents the minimum possible radiation benefit (a 10-year risk of local recurrence of 0.15 and 30% of recurrences consisting of invasive disease).

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Figure 3. Two-way sensitivity analyses are illustrated for overall survival benefit with radiation therapy varying the risk of local recurrence (LR) without radiation therapy and the proportion of LR that is noninvasive disease for the 3 age cohorts. The proportion of LR that is invasive disease varies on the y-axis, and the risk of LR at 10 years is represented on the x-axis for the cohorts (A) aged 45 years, (B) aged 60 years, and (C) aged 75 years. Blue areas represent the combinations of values for which the survival benefit from radiation therapy is <3 months, yellow areas represent the combinations of values for which the survival benefit from radiation therapy is between 3 months and 6 months, and pink areas represent the combinations of values for which the survival benefit from radiation therapy is >6 months. The analyses indicate that, as the proportion of LR that is invasive disease and/or the risk of LR without radiation increases, the benefit increases. For the cohort aged 60 years, all possible combinations result in a benefit <4 months. For the cohort aged 75 years, all combinations lead to a benefit <2 months.

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In a threshold analysis, we observed that the radiation therapy strategy decreases the likelihood of lifetime breast preservation unless the chance of mastectomy after recurrence or a new cancer diagnosis exceeds 66% for women aged 60 years (Fig. 4). A 2-way sensitivity analysis revealed that excision alone resulted in the higher likelihood of breast preservation unless the chance of mastectomy after recurrence or a new cancer diagnosis was high (Fig. 5). The threshold mastectomy likelihood in a previously nonirradiated breast at which radiation therapy resulted in greater breast preservation was relatively insensitive to an absolute recurrence risk >0.10 at 10 years (Fig. 5).

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Figure 4. This chart represents a sensitivity analysis for the likelihood of mastectomy at the time of recurrence or new diagnosis on lifetime breast preservation for a woman aged 60 years at diagnosis. The percentage change in lifetime breast preservation with radiation therapy (y-axis) varies with the likelihood of mastectomy at the time of recurrence or new breast cancer (x-axis) in a previously nonirradiated breast. Radiation therapy is associated with a reduction in lifetime breast preservation unless the likelihood of mastectomy at the time of recurrence or new breast cancer exceeds 66% (baseline stage-weighted average, 32%).

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thumbnail image

Figure 5. This chart represents a 2-way sensitivity analysis for maximizing lifetime breast preservation varying the likelihood of mastectomy (mtx) at the time of recurrence or new diagnosis and the risk of recurrence without radiation therapy for a woman aged 60 years at diagnosis. The analysis indicates that the strategy that maximizes lifetime breast preservation varies with the absolute likelihood of recurrence on the y-axis and the likelihood of needing mastectomy for a new diagnosis in a previously nonirradiated breast on the x-axis. The green area indicates those combinations of the 2 likelihoods in which radiation therapy maximizes breast preservation, and the blue area indicates the combinations of likelihoods in which excision alone maximizes breast preservation.

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DISCUSSION

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. FUNDING SOURCES
  7. CONFLICT OF INTEREST DISCLOSURES
  8. REFERENCES

Clinical trials of radiation therapy for DCIS have not been powered to detect survival differences between the treatment arms, and their length of follow-up is insufficient to evaluate lifetime breast preservation. Therefore, we used a decision analysis to model the downstream implications of recurrence after DCIS to gain insights into the tradeoffs associated with radiation. Our model suggests that the addition of radiation therapy after excision for DCIS results in modest improvements in invasive disease-free and overall survival, with declining benefits as age at diagnosis increases. However, the likelihood of long-term breast conservation is lower with radiation, because women who receive it generally are committed to mastectomy after any local recurrence or new cancer diagnosis in the treated breast.

In our model, the survival benefit with radiation therapy is a consequence of the reduced risk of an invasive local recurrence and is a credible finding given the proven effects of radiation on the subsequent development of invasive recurrence and of invasive cancer recurrence on survival.17 Our analysis demonstrates that the magnitude of this benefit is very small, a finding consistent with the lack of difference observed in randomized trials that have assessed radiation for DCIS23 and with previous DCIS modeling efforts.24

The key question raised by our results is whether an invasive disease-free and overall survival benefit is sufficient to justify the routine recommendation of radiation therapy for all women with DCIS. An improvement in invasive disease-free survival translates into a lower probability of a new cancer diagnosis and the resulting need for further surgery and possibly adjuvant chemotherapy. And an overall survival advantage is an even more compelling potential benefit. But these benefits must be weighed not only against the inconvenience and potential side effects of radiation but also against the reduced probability of maintaining intact breasts over a lifetime. The magnitude of the likely survival advantage is a critical consideration in weighing these risks and benefits. A previous modeling analysis estimated that prophylactic mastectomy among women ages 30 to 60 years without elevated breast cancer risk added approximately 6 months of additional life expectancy, which is a more substantial benefit than we observed in any age group.25 Yet we do not routinely recommend prophylactic mastectomy to women with even a markedly elevated breast cancer risk, and we certainly do not recommend it to women at average risk. Instead, prophylactic mastectomy is uniformly considered to be a preference-sensitive decision. Our results suggest that the decision about whether to include radiation after excision of DCIS also is most appropriately considered a preference-sensitive decision. Women should be fully informed about the expected outcomes of the alternative treatment strategies, including the risks of both death from breast cancer and eventual mastectomy, and they should be encouraged to choose the strategy that is most consistent with their own values and preferences.

Our current analysis has limitations inherent to all modeling analyses. It was necessary to make a limited number of assumptions about the natural history and treatment of disease to specify a finite number of clinical states. However, most assumptions that we used applied to both treatment arms, excision alone and excision plus radiation therapy; therefore, they were unlikely to bias the analysis. We used estimates derived from the literature or databases to inform our baseline analysis and observed that the model results were robust across a wide range of values for key parameters in sensitivity analyses.

No population-based data are available on the proportion of women who choose mastectomy for recurrence or new cancer after previous DCIS treatment that did not include radiation. Therefore, we extrapolated the likelihood of mastectomy by stage from treatment patterns among patients newly diagnosed with cancer in a previously nonirradiated breast (average, 32%). This average was close to that reported by a prospective study of excision alone for DCIS in which the likelihood of mastectomy at the time of recurrence was 31%.12 Our likelihood actually may overestimate the probability of mastectomy if 1 of the primary reasons a woman would opt to forego radiation for DCIS is the desire to maximize the likelihood of breast preservation. In our sensitivity analysis, we included the 48% likelihood of mastectomy observed in an early report on treatment patterns for local recurrence in the excision-alone arm of the NSABP B-17 DCIS trial26; and we observed that, even at this rate, the radiation strategy decreased the likelihood of breast preservation. In fact, even if the probability were much higher than in our baseline analysis, as long is it did not exceed 66%, our sensitivity analysis indicates that the no-radiation strategy would result in a higher rate of breast preservation.

However, if local control rates with radiation therapy in the setting of recurrent DCIS after excision alone are inferior to those achieved with new diagnosis of DCIS or if breast-preserving surgery is possible after a new diagnosis in a previously irradiated breast,27, 28 then the decrement in breast preservation with radiation therapy for DCIS would be mitigated. Moreover, if a patient is ineligible for repeat breast-conserving surgery because of anatomic constraints at the time of a new diagnosis in a previously nonradiated breast or if she would not elect breast preservation even if it were possible, then the radiation therapy arm would maximize her likelihood of breast preservation. However, our model also indicates that, for those patients who would not have experienced a local recurrence after breast-conserving surgery alone, radiation therapy comes at a cost—they are at risk of having a second primary breast cancer, and their history of prior radiation most often precludes breast-conserving options.

We also did not study the effect of adding tamoxifen to radiation therapy.9, 21 However, unless tamoxifen eliminated all recurrences, it would not change the fundamental nature of the tradeoffs we describe. Finally, we did not model outcomes after mastectomy for DCIS, because our objective was to compare alternative breast-conserving surgical strategies. It is easy to extrapolate from our findings, however, because mastectomy would result in even lower local recurrence rates, with resulting improvement in invasive-free survival, while reducing the likelihood of breast preservation to zero.

Currently, approximately 50% of patients receive radiation after excision for DCIS with evidence of wide regional variation in practice patterns, suggesting a lack of consensus regarding the use of radiation therapy.2, 15 Much of the debate surrounding the decision to add radiation for DCIS has focused on the absolute risk of recurrence without radiation. Our results suggest that this decision should be determined by patient preferences for women who are at average risk of recurrence. Our model also provides some insight into the role of radiation therapy in women whose constellation of clinical and biologic factors places them at the highest risk of recurrence.23, 29, 30 Our sensitivity analyses reveal that, among the highest recurrence risk group, the survival benefits with radiation indeed do increase, whereas the harms of radiation therapy, in terms of lower rates of long-term breast preservation, remain relatively stable. However, even in this group, the magnitude of the benefit conferred by radiation remains quite modest, suggesting that a decision-making paradigm that emphasizes patient preferences is appropriate in all risk groups.

Our analysis demonstrates that the decision to add radiation therapy is essentially a toss-up and suggests that more trials with longer follow-up will not change what can be learned from a relatively simple and transparent analysis of existing data. Radiation for DCIS is prophylactic; it reduces the risk of invasive recurrence, which is the only lethal form of breast cancer, while increasing the probability of eventual mastectomy. The absolute magnitude of both effects is modest, such that personal patient preferences should drive decision making. Express delineation of the tradeoffs associated with radiation therapy may help guide treatment decisions that are consonant with patient preferences, with the result that variation in care reflects those individual preferences rather than the biases of treating physicians.

FUNDING SOURCES

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. FUNDING SOURCES
  7. CONFLICT OF INTEREST DISCLOSURES
  8. REFERENCES

This research was supported by a Career Development Award from the National Institutes of Health (1K07 CA118269 to R.S.P.).

REFERENCES

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. FUNDING SOURCES
  7. CONFLICT OF INTEREST DISCLOSURES
  8. REFERENCES
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    Fisher B, Dignam J, Wolmark N, et al. Tamoxifen in treatment of intraductal breast cancer: National Surgical Adjuvant Breast and Bowel Project B-24 randomised controlled trial. Lancet. 1999; 353: 1993-2000.
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    Arias E. United States life tables, 2004. Natl Vital Stat Rep. 2007; 56: 1-39.
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