lunes, 8 de abril de 2019

Breast Cancer Treatment (PDQ®) 5/5 —Health Professional Version - National Cancer Institute

Breast Cancer Treatment (PDQ®)—Health Professional Version - National Cancer Institute

National Cancer Institute



Breast Cancer Treatment (PDQ®)–Health Professional Version

Chemotherapy

Patients on hormone therapy whose tumors have progressed are candidates for cytotoxic chemotherapy. There are no data suggesting that combination therapy results in an OS benefit over single-agent therapy. Patients with hormone receptor-negative tumors and those with visceral metastases or symptomatic disease are also candidates for cytotoxic agents.[60]
Single agents that have shown activity in metastatic breast cancer include the following:
  • Anthracyclines.
    • Doxorubicin.
    • Epirubicin.
    • Liposomal doxorubicin.[61-64]
    • Mitoxantrone.
  • Taxanes.
    • Paclitaxel.[65,66]
    • Docetaxel.
    • Albumin-bound nanoparticle paclitaxel (ABI-007 or Abraxane).[67,68]
  • Alkylating agents.
    • Cyclophosphamide.
  • Fluoropyrimidines.
    • Capecitabine.[69-71]
    • 5-Fluorouracil (5-FU).
  • Antimetabolites.
    • Methotrexate.
  • Vinca alkaloids.
    • Vinorelbine.[72]
    • Vinblastine.
    • Vincristine.
  • Platinum.
    • Carboplatin.
    • Cisplatin.
  • Other.
    • Gemcitabine.[73]
    • Mitomycin C.
    • Eribulin mesylate.[74,75]
    • Ixabepilone.[76]
Combination regimens that have shown activity in metastatic breast cancer include the following:
  • AC: Doxorubicin and cyclophosphamide.[77]
  • EC: Epirubicin and cyclophosphamide.[78]
  • Docetaxel and doxorubicin.[79]
  • CAF: Cyclophosphamide, doxorubicin, and 5-FU.[80]
  • CMF: Cyclophosphamide, methotrexate, and 5-FU.[81]
  • Doxorubicin and paclitaxel.[82,83]
  • Docetaxel and capecitabine.[84]
  • Vinorelbine and epirubicin.[85]
  • Capecitabine and ixabepilone.[86]
  • Carboplatin and gemcitabine.[87]
  • Gemcitabine and paclitaxel.[88]
There are no data suggesting that combination therapy results in an OS benefit over single-agent therapy. An Eastern Cooperative Oncology intergroup study (E-1193) randomly assigned patients to receive paclitaxel and doxorubicin, given both as a combination and sequentially.[89] Although response rate and time to disease progression were both better for the combination, survival was the same in both groups.[89][Level of evidence: 1iiA]; [90,91]
The selection of therapy in individual patients is influenced by the following:
  • Rate of disease progression.
  • Presence or absence of comorbid medical conditions.
  • Physician/patient preference.
Currently, no data support the superiority of any particular regimen. Sequential use of single agents or combinations can be used for patients who relapse with metastatic disease. Combination chemotherapy is often given if there is evidence of rapidly progressive disease or visceral crisis. Combinations of chemotherapy and hormone therapy have not shown an OS advantage over the sequential use of these agents.[1,92] A systematic review of 17 randomized trials found that the addition of one or more chemotherapy drugs to a chemotherapy regimen in the attempt to intensify the treatment improved tumor response but had no effect on OS.[93][Level of evidence: 1iiA]
Decisions regarding the duration of chemotherapy may consider the following:
  • Patient preference and goals of treatment.
  • Presence of toxicities from previous therapies.
  • Availability of alternative treatment options.
The optimal time for patients with responsive or stable disease has been studied by several groups. For patients who attain a complete response to initial therapy, two randomized trials have shown a prolonged DFS after immediate treatment with a different chemotherapy regimen compared with observation and treatment upon relapse.[94,95][Level of evidence: 1iiA] Neither of these studies, however, showed an improvement in OS for patients who received immediate treatment; in one of these studies,[95] survival was actually worse in the group that was treated immediately. Similarly, no difference in survival was noted when patients with partial response or stable disease after initial therapy were randomly assigned to receive either a different chemotherapy versus observation [96] or a different chemotherapy regimen given at higher versus lower doses.[97][Level of evidence: 1iiA] However, 324 patients who achieved disease control were randomly assigned to maintenance chemotherapy or observation. Patients who received maintenance chemotherapy (paclitaxel and gemcitabine) had improved PFS at 6 months and improved OS. This was associated with an increased rate of adverse events.[98][Level of evidence: 1iiA] Because there is no standard approach for treating metastatic disease, patients requiring second-line regimens are good candidates for clinical trials.

Chemotherapy plus immunotherapy

The addition of atezolizumab, an anti-programmed death ligand 1 (PD-L1) + antibody, to first-line chemotherapy for patients with hormone-receptor–negative and human epidermal growth factor receptor 2 (HER2)–negative advanced breast cancer was evaluated in the phase III randomized placebo-controlled IMpassion130 trial (NCT02425891).[99] Participants (N = 902) were randomly assigned 1:1 to atezolizumab plus nanoparticle albumin-bound (nab)-paclitaxel or to placebo plus nab-paclitaxel. Participants were stratified according to the presence of liver metastases (yes/no), receipt of previous taxane therapy (yes/no), and PD-L1 status (positive or negative). PD-L1 score of 1% or greater was defined as positive. Co-primary endpoints included PFS and OS, both of which were evaluated in the intention-to-treat population and in the PD-L1–positive population (n = 369).
  1. PFS data are final with a median follow-up of 12.9 months and included the following:
    • In the intention-to-treat population, PFS was improved with the addition of atezolizumab (median PFS, 7.2 months vs. 5.5 months; HR, 0.80; 95% CI, 0.69–0.92; P = .0025).
    • In the PD-L1–positive population, PFS was improved with the addition of atezolizumab (median PFS, 7.5 months vs. 5 months; HR, 0.62; 95% CI, 0.49–0.78; P < .001).
  2. OS data are not yet mature. Results of the first interim analysis for OS, performed at the time of the final PFS analysis, included the following:
    • In the intention-to-treat population, there was a nonsignificant trend towrd improved OS with the addition of atezolizumab (median OS, 21.3 months vs. 17.6 months; HR, 0.84; 95% CI, 0.69–1.02; P = .08).
    • The study design used hierarchical testing for OS requiring that the OS be statistically significantly improved with atezolizumab in the intention-to-treat population before OS could be compared between the arms in the PD-L1–positive population. Because this requirement was not met at the time of the first interim analysis, a P-value could not be determined at that time for the comparison of OS between the two arms in the PD-L1–positive population. Median OS was, however, 9.5 months longer in the atezolizumab arm in the PD-L1–positive population (25 months vs. 15.5 months; HR, 0.62; 95% CI, 0.45–0.86).[99][Level of evidence: 1iDiii]
  3. Adverse events occurred as expected. Adverse events that were potentially immune-related were more frequent in the atezolizumab arm.
Atezolizumab is not currently approved by the FDA for use in breast cancer in the United States.

Cardiac toxic effects with anthracyclines

The potential for anthracycline-induced cardiac toxic effects should be considered in the selection of chemotherapeutic regimens for selected patients. Recognized risk factors for cardiac toxicity include the following:
  • Advanced age.
  • Previous chest-wall radiation therapy.
  • Previous anthracycline exposure.
  • Hypertension and known underlying heart disease.
  • Diabetes.
The cardioprotective drug dexrazoxane has been shown to decrease the risk of doxorubicin-induced cardiac toxicity in patients in controlled studies. The use of this agent has permitted patients to receive higher cumulative doses of doxorubicin and has allowed patients with cardiac risk factors to receive doxorubicin.[100-103] The risk of cardiac toxicity may also be reduced by administering doxorubicin as a continuous intravenous infusion.[104] The American Society of Clinical Oncology guidelines suggest the use of dexrazoxane in patients with metastatic cancer who have received a cumulative dose of doxorubicin of 300 mg/m2 or more when further treatment with an anthracycline is likely to be of benefit.[105] Dexrazoxane has a similar protective effect in patients receiving epirubicin.[106]

Surgery

Surgery may be indicated for select patients. For example, patients may need surgery if the following issues occur:
  • Fungating/painful breast lesions (mastectomy).
  • Parenchymal brain or vertebral metastases with spinal cord compression.
  • Isolated lung metastases.
  • Pathologic (or impending) fractures.
  • Pleural or pericardial effusions.
(Refer to the PDQ summary on Cancer Pain for more information; refer to the PDQ summary on Cardiopulmonary Syndromes for information about pleural and pericardial effusions.)

Radiation Therapy

Radiation therapy has a major role in the palliation of localized symptomatic metastases.[107] Indications for external-beam radiation therapy include the following:
  • Painful bony metastases.
  • Unresectable central nervous system metastases (i.e., brain, meninges, and spinal cord).
  • Bronchial obstruction.
  • Fungating/painful breast or chest wall lesions.
  • After surgery for decompression of intracranial or spinal cord metastases.
  • After fixation of pathologic fractures.
Strontium chloride Sr 89, a systemically administered radionuclide, can be administered for palliation of diffuse bony metastases.[108,109]

Bone Modifier Therapy

The use of bone modifier therapy to reduce skeletal morbidity in patients with bone metastases should be considered.[110] Results of randomized trials of pamidronate and clodronate in patients with bony metastatic disease show decreased skeletal morbidity.[111-113][Level of evidence: 1iC] Zoledronate has been at least as effective as pamidronate.[114]
The optimal dosing schedule for zoledronate was studied in CALGB-70604 [Alliance; NCT00869206], which randomly assigned 1,822 patients, 855 of whom had metastatic breast cancer, to receive zoledronic acid every 4 weeks or every 12 weeks.[115] Skeletal-related events were similar in both groups, with 260 patients (29.5%) in the zoledronate every-4-week dosing group and 253 patients (28.6%) in the zoledronate every-12-week dosing group experiencing at least one skeletal-related event (risk difference of -0.3% [1-sided 95% CI, -4% to infinity]; P < .001 for noninferiority).[115][Level of evidence: 1iiD] This study suggests that the longer dosing interval of zoledronate every 12 weeks is a reasonable treatment option.
The monoclonal antibody denosumab inhibits the receptor activator of nuclear factor kappa beta ligand (RANKL). A meta-analysis of three phase III trials (NCT00321464, NCT00321620, and NCT00330759) comparing zoledronate versus denosumab for management of bone metastases suggests that denosumab is similar to zoledronate in reducing the risk of a first skeletal-related event.[116]
(Refer to the PDQ summary on Cancer Pain for more information on bisphosphonates.)

Bevacizumab

Bevacizumab is a humanized monoclonal antibody directed against all isoforms of vascular endothelial growth factor–A. Its role in the treatment of metastatic breast cancer remains controversial.
Evidence (bevacizumab for metastatic breast cancer):
  1. The efficacy and safety of bevacizumab as a second- and third-line treatment for patients with metastatic breast cancer were studied in a single, open-label, randomized trial.[117] The study enrolled 462 patients who had received previous anthracycline and taxane therapy and were randomly assigned to receive capecitabine with or without bevacizumab.[117][Level of evidence: 1iiA]
    • The study failed to demonstrate a statistically significant effect on PFS (4.9 months with combination therapy vs. 4.2 months with capecitabine alone; HR, 0.98) or OS (15.1 months vs. 14.5 months).[117][Level of Evidence: 1iiA]
  2. ECOG-2100 (NCT00028990), an open-label, randomized, phase III trial, compared paclitaxel alone with paclitaxel and bevacizumab.[118][Level of evidence: 1iiA]
    • The trial demonstrated that the addition of bevacizumab to paclitaxel significantly prolonged median PFS compared with paclitaxel alone as the initial treatment for patients with metastatic breast cancer (11.8 months vs. 5.9 months; HR, 0.60; P < .001).[118][Level of Evidence: 1iiA]
    • The addition of bevacizumab did not improve OS (26.7 months vs. 25.2 months; P = .16).
    • Notably, patients treated on the bevacizumab-containing arm had significantly higher rates of severe hypertension, proteinuria, cerebrovascular ischemia, and infection.
  3. The AVADO (NCT00333775) trial randomly assigned 736 patients to receive docetaxel plus either placebo or bevacizumab at 7.5 mg/kg or 15 mg/kg every 3 weeks as the initial treatment for patients with metastatic breast cancer.[119][Level of evidence: 1iiA]
    • The combination of docetaxel plus bevacizumab at 15 mg/kg, but not 7.5 mg/kg, modestly improved median PFS compared with placebo (10.1 mo vs. 8.1 mo) but did not improve OS (30.2 months vs. 31.9 months; P = .85).[119][Level of Evidence: 1iiA]
    • More toxicity was seen in patients in the bevacizumab-containing arms, with significantly higher rates of bleeding and hypertension compared with patients in the placebo arms.
  4. The RIBBON 1 (NCT00262067) trial randomly assigned 1,237 patients in a 2:1 fashion to receive either standard chemotherapy plus bevacizumab or standard chemotherapy plus placebo.[120][Level of evidence: 1iiA]
    • Median PFS was longer for each bevacizumab-containing combination (capecitabine cohort: increased from 5.7 months to 8.6 months; HR, 0.69; 95% CI, 0.56–0.84; log-rank, P < .001; and taxane-anthracycline cohort: increased from 8.0 months to 9.2 months; HR, 0.64; 95% CI, 0.52–0.80; log-rank, P < .001).[120][Level of Evidence: 1iiA]
    • No statistically significant differences in OS between the placebo- and bevacizumab-containing arms were observed.
    • Toxicities associated with bevacizumab were similar to those seen in previous bevacizumab clinical trials.
  5. The RIBBON 2 (NCT00281697) trial studied the efficacy of bevacizumab as a second-line treatment for metastatic breast cancer. This trial randomly assigned 684 patients in a 2:1 fashion to receive either standard chemotherapy plus bevacizumab or standard chemotherapy plus placebo.[121][Level of evidence: 1iA]
    • Median PFS increased from 5.1 to 7.2 months for the bevacizumab-containing treatment arm (stratified HR for PFS, 0.78; 95% CI, 0.64–0.93; P = .0072).
    • However, no statistically significant difference in OS was seen (16.4 months for chemotherapy plus placebo vs. 18.0 months for chemotherapy plus bevacizumab, P = .3741).[121][Level of evidence: 1iA]
    • Toxicities associated with bevacizumab were similar to those seen in previous clinical trials.
In November 2011, because of the consistent finding that bevacizumab improved PFS only modestly but did not improve OS, and given bevacizumab’s considerable toxicity profile, the FDA revoked approval of bevacizumab for the treatment of metastatic breast cancer.

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.
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  84. O'Shaughnessy J, Miles D, Vukelja S, et al.: Superior survival with capecitabine plus docetaxel combination therapy in anthracycline-pretreated patients with advanced breast cancer: phase III trial results. J Clin Oncol 20 (12): 2812-23, 2002. [PUBMED Abstract]
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  87. O'Shaughnessy J, Schwartzberg L, Danso MA, et al.: Phase III study of iniparib plus gemcitabine and carboplatin versus gemcitabine and carboplatin in patients with metastatic triple-negative breast cancer. J Clin Oncol 32 (34): 3840-7, 2014. [PUBMED Abstract]
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Ductal Carcinoma In Situ

Introduction

Ductal carcinoma in situ (DCIS) is a noninvasive condition. DCIS can progress to invasive cancer, but estimates of the probability of this vary widely. Some reports include DCIS in breast cancer statistics. In 2015, DCIS is expected to account for about 16% of all newly diagnosed invasive plus noninvasive breast tumors in the United States.[1] For invasive and noninvasive tumors detected by screening, DCIS accounts for approximately 25% of all cases.
The frequency of a DCIS diagnosis has increased markedly in the United States since the use of screening mammography became widespread. Very few cases of DCIS present as a palpable mass, with more than 90% being diagnosed by mammography alone.[2]
DCIS comprises a heterogeneous group of histopathologic lesions that have been classified into the following subtypes primarily because of architectural pattern:
  • Micropapillary.
  • Papillary.
  • Solid.
  • Cribriform.
  • Comedo.
Comedo-type DCIS consists of cells that appear cytologically malignant, with the presence of high-grade nuclei, pleomorphism, and abundant central luminal necrosis. Comedo-type DCIS appears to be more aggressive, with a higher probability of associated invasive ductal carcinoma.[3]

Treatment Options for Patients With DCIS

Treatment options for DCIS include the following:
  1. Breast-conserving surgery or mastectomy plus radiation therapy with or without tamoxifen.
  2. Total mastectomy with or without tamoxifen.
In the past, the customary treatment for DCIS was mastectomy.[4] The rationale for mastectomy included a 30% incidence of multicentric disease, a 40% prevalence of residual tumor at mastectomy after wide excision alone, and a 25% to 50% incidence of in-breast recurrence after limited surgery for palpable tumor, with 50% of those recurrences being invasive carcinoma.[4,5] The combined local and distant recurrence rate after mastectomy is 1% to 2%. No randomized comparisons of mastectomy versus breast-conserving surgery plus breast radiation therapy are available.
Because breast-conserving surgery combined with breast radiation therapy is successful for invasive carcinoma, this conservative approach was extended to DCIS. To determine whether breast-conserving surgery plus radiation therapy was a reasonable approach to the management of DCIS, the National Surgical Adjuvant Breast and Bowel Project (NSABP) and the European Organisation for Research and Treatment of Cancer (EORTC) have each completed prospective randomized trials in which women with localized DCIS and negative surgical margins after excisional biopsy were randomly assigned to receive either breast radiation therapy (50 Gy) or no further therapy.[6-9]
Evidence (breast-conserving surgery plus radiation therapy to the breast):
  1. Of the 818 women enrolled in the NSABP-B-17 trial, 80% were diagnosed by mammography, and 70% of the patients' lesions were 1 cm or smaller. Results were reported at the 12-year actuarial follow-up interval.[7]; [9][Level of evidence: 1iiDii]
    • The overall rate of in-breast tumor recurrence was reduced from 31.7% to 15.7% when radiation therapy was delivered (P < .005).
    • Radiation therapy reduced the occurrence of invasive cancer from 16.8% to 7.7% (P = .001) and recurrent DCIS from 14.6% to 8.0% (P = .001).
    • Nine pathologic features were evaluated for their ability to predict for in-breast recurrence, but only comedo necrosis was determined to be a significant predictor for recurrence.
  2. Similarly, of the 1,010 patients enrolled in the EORTC-10853 trial, mammography detected lesions in 71% of the women. Results were reported at a median follow-up of 10.5 years.[9][Level of evidence: 1iiDii]
    • The overall rate of in-breast tumor recurrence was reduced from 26% to 15% (P< .001), with a similarly effective reduction of invasive recurrence rates (13% to 8%, P = .065) and noninvasive recurrence rates (14% to 7%, P = .001).
    • In this analysis, parameters associated with an increased risk of in-breast recurrence included age 40 years or younger, palpable disease, intermediate or poorly differentiated DCIS, cribriform or solid growth pattern, and indeterminate margins. Elsewhere, margins of less than 1 mm have been associated with an unacceptable local recurrence rate, even with radiation therapy.[10]
    In both studies, the effect of radiation therapy was consistent across all assessed risk factors.
  3. The benefit of administering radiation therapy has been confirmed in a systematic review of four randomized trials (hazard ratio [HR], 0.49; 95% confidence interval [CI], 0.41–0.58; P < .00001). In this study, the number needed to treat with radiation therapy was nine women to prevent one ipsilateral breast recurrence.[11]
  4. A large national clinical trial by the Radiation Therapy Oncology Group (RTOG-9804[NCT00003857]) comparing breast-conserving surgery and tamoxifen with or without radiation therapy was closed because of poor accrual (636 of planned 1,790 patients accrued). Patients with good-risk DCIS (defined as mammographically detected low- or intermediate-grade DCIS, measuring less than 2.5 cm with margins of 3 mm or more) were enrolled.[12]
    • With a median follow-up of 7 years, the ipsilateral local failure rate was low with observation (6.7%; 95% CI, 3.2%–9.6%) but was decreased significantly with the addition of radiation therapy (0.9%; 95% CI, 0.0%–2.2%).[12]
The results of the NSABP-B-17 and EORTC-10853 trials plus two others were included in a meta-analysis that demonstrated reductions in all ipsilateral breast events (HR, 0.49; 95% CI, 0.41–0.58; P < .00001), ipsilateral invasive recurrence (HR, 0.50; 95% CI, 0.32–0.76; P = .001), and ipsilateral DCIS recurrence (HR, 0.61; 95% CI, 0.39–0.95; P = .03).[13][Level of evidence: 1iiD] After 10 years of follow-up, there was, however, no significant effect on breast cancer mortality, mortality from causes other than breast cancer, or all-cause mortality.[11]
To identify a favorable group of patients for whom postoperative radiation therapy could be omitted, several pathologic staging systems have been developed and tested retrospectively, but consensus recommendations have not been achieved.[14-17]
The Van Nuys Prognostic Index is one pathologic staging system that combines three predictors of local recurrence (i.e., tumor size, margin width, and pathologic classification). It was used to retrospectively analyze 333 patients treated with either excision alone or excision and radiation therapy.[17] Using this prognostic index, patients with favorable lesions who received surgical excision alone had a low recurrence rate (i.e., 2%, with a median follow-up of 79 months). A subsequent analysis of these data was performed to determine the influence of margin width on local control.[18] Patients whose excised lesions had margin widths of 10 mm or more in every direction had an extremely low probability of local recurrence with surgery alone (4%, with a mean follow-up of 8 years).
Both reviews are retrospective, noncontrolled, and subject to substantial selection bias. In contrast, the prospective NSABP trial did not identify any subset of patients who did not benefit from the addition of radiation therapy to breast-conserving surgery in the management of DCIS.[3,6,13,19]
To determine whether tamoxifen adds to the efficacy of local therapy in the management of DCIS, the NSABP performed a double-blind prospective trial (NSABP-B-24).
Evidence (adjuvant endocrine therapy):
  1. In NSABP-B-24, 1,804 women were randomly assigned to receive breast-conserving surgery, radiation therapy (50 Gy), and placebo or breast-conserving surgery, radiation therapy, and tamoxifen (20 mg qd for 5 years).[20] Positive or unknown surgical margins were present in 23% of patients. Approximately 80% of the lesions measured ≤1 cm, and more than 80% were detected mammographically. Breast cancer events were defined as the presence of new ipsilateral disease, contralateral disease, or metastases.
    • Women in the tamoxifen group had fewer breast cancer events at 5 years than did those treated with a placebo (8.2% vs. 13.4%; P = .009).[20][Level of evidence: 1iDii]
    • With tamoxifen, ipsilateral invasive breast cancer decreased from 4.2% to 2.1% at 5 years (P = .03).
    • Tamoxifen also decreased the incidence of contralateral breast neoplasms (invasive and noninvasive) from 0.8% per year to 0.4% per year (P = .01).
    • The benefit of tamoxifen extended to patients with positive or uncertain margins.[21] (Refer to the PDQ summary on Breast Cancer Prevention for more information.)
    • No survival advantage was demonstrated for the use of tamoxifen.
  2. In NSABP-B-24, 1,804 women were randomly assigned to receive breast-conserving surgery, radiation therapy (50 Gy), and placebo or breast-conserving surgery, radiation therapy, and tamoxifen (20 mg qd for 5 y).[20] Positive or unknown surgical margins were present in 23% of patients. Approximately 80% of the lesions measured ≤1 cm, and more than 80% were detected mammographically. Breast cancer events were defined as the presence of new ipsilateral disease, contralateral disease, or metastases.
    • No survival advantage was demonstrated for the use of tamoxifen.
  3. In the NSABP-B35 double-blind study, 3,104 postmenopausal women with DCIS who were treated with breast-conserving surgery were randomly assigned to receive either adjuvant tamoxifen or anastrozole, in addition to adjuvant radiation therapy.
    • The use of anastrozole was associated with significantly fewer breast cancer events (HR, 0.73; P = .023) but no improvement in survival.[22][Level of evidence: 1iDi]
  4. The Second International Breast Cancer Intervention Study (IBIS II DCIS[NCT00078832]) trial enrolled 2,980 postmenopausal women in a double-blind comparison of tamoxifen with anastrozole as adjuvant therapy. All of the women had breast conserving surgery, and 71% of them had radiation therapy.[23]
    • No difference in the rate of breast cancer recurrence in favor of anastrozole was found (HR, 0.89; 95% CI, 0.64–1.23; P = .49), and there was no difference in survival.
The decision to prescribe endocrine therapy after a diagnosis of DCIS often involves a discussion with the patient about the potential benefits and side effects of each agent.

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.
References
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  11. Correa C, McGale P, Taylor C, et al.: Overview of the randomized trials of radiotherapy in ductal carcinoma in situ of the breast. J Natl Cancer Inst Monogr 2010 (41): 162-77, 2010. [PUBMED Abstract]
  12. McCormick B, Winter K, Hudis C, et al.: RTOG 9804: a prospective randomized trial for good-risk ductal carcinoma in situ comparing radiotherapy with observation. J Clin Oncol 33 (7): 709-15, 2015. [PUBMED Abstract]
  13. Goodwin A, Parker S, Ghersi D, et al.: Post-operative radiotherapy for ductal carcinoma in situ of the breast. Cochrane Database Syst Rev 11: CD000563, 2013. [PUBMED Abstract]
  14. Page DL, Lagios MD: Pathologic analysis of the National Surgical Adjuvant Breast Project (NSABP) B-17 Trial. Unanswered questions remaining unanswered considering current concepts of ductal carcinoma in situ. Cancer 75 (6): 1219-22; discussion 1223-7, 1995. [PUBMED Abstract]
  15. Fisher ER, Costantino J, Fisher B, et al.: Response - blunting the counterpoint. Cancer 75 (6): 1223-1227, 1995.
  16. Holland R, Peterse JL, Millis RR, et al.: Ductal carcinoma in situ: a proposal for a new classification. Semin Diagn Pathol 11 (3): 167-80, 1994. [PUBMED Abstract]
  17. Silverstein MJ, Lagios MD, Craig PH, et al.: A prognostic index for ductal carcinoma in situ of the breast. Cancer 77 (11): 2267-74, 1996. [PUBMED Abstract]
  18. Silverstein MJ, Lagios MD, Groshen S, et al.: The influence of margin width on local control of ductal carcinoma in situ of the breast. N Engl J Med 340 (19): 1455-61, 1999. [PUBMED Abstract]
  19. Goodwin A, Parker S, Ghersi D, et al.: Post-operative radiotherapy for ductal carcinoma in situ of the breast--a systematic review of the randomised trials. Breast 18 (3): 143-9, 2009. [PUBMED Abstract]
  20. 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 353 (9169): 1993-2000, 1999. [PUBMED Abstract]
  21. Houghton J, George WD, Cuzick J, et al.: Radiotherapy and tamoxifen in women with completely excised ductal carcinoma in situ of the breast in the UK, Australia, and New Zealand: randomised controlled trial. Lancet 362 (9378): 95-102, 2003. [PUBMED Abstract]
  22. Margolese RG, Cecchini RS, Julian TB, et al.: Anastrozole versus tamoxifen in postmenopausal women with ductal carcinoma in situ undergoing lumpectomy plus radiotherapy (NSABP B-35): a randomised, double-blind, phase 3 clinical trial. Lancet 387 (10021): 849-56, 2016. [PUBMED Abstract]
  23. Forbes JF, Sestak I, Howell A, et al.: Anastrozole versus tamoxifen for the prevention of locoregional and contralateral breast cancer in postmenopausal women with locally excised ductal carcinoma in situ (IBIS-II DCIS): a double-blind, randomised controlled trial. Lancet 387 (10021): 866-73, 2016. [PUBMED Abstract]

Changes to This Summary (03/15/2019)

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.
General Information About Breast Cancer
Updated statistics with estimated new cases and deaths for 2019 (cited American Cancer Society as reference 1).
Stage Information for Breast Cancer
This section was extensively revised.
Locoregional Recurrent Breast Cancer
Revised text to state that in estrogen‒receptor (ER)-negative patients, the hazard ratio (HR) for disease-free survival (DFS) for chemotherapy versus no chemotherapy was 0.29, whereas in ER-positive patients, the HR was 1.07. Added that this trial supports consideration of adjuvant chemotherapy after complete resection of isolated locoregional recurrence of breast cancer in patients with ER-negative tumors.
Metastatic Breast Cancer
Added text about palbociclib in the Paloma-3 trial to state that a prespecified analysis of overall survival (OS) was made after 310 patients had died. A 6.9 month difference in median OS favoring the palbociclib-fulvestrant arm was found, which did not reach statistical significance (cited Turner et al. as reference 36).
Added Chemotherapy plus immunotherapy as a new subsection.
This summary is written and maintained by the PDQ Adult Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® - NCI's Comprehensive Cancer Database pages.

About This PDQ Summary

Purpose of This Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of breast cancer. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.

Reviewers and Updates

This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).
Board members review recently published articles each month to determine whether an article should:
  • be discussed at a meeting,
  • be cited with text, or
  • replace or update an existing article that is already cited.
Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.
The lead reviewers for Breast Cancer Treatment are:
  • Joseph L. Pater, MD (NCIC-Clinical Trials Group)
  • Karen L. Smith, MD, MPH (Johns Hopkins University at Sibley Memorial Hospital)
Any comments or questions about the summary content should be submitted to Cancer.gov through the NCI website's Email Us. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.

Levels of Evidence

Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Adult Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.

Permission to Use This Summary

PDQ is a registered trademark. Although the content of PDQ documents can be used freely as text, it cannot be identified as an NCI PDQ cancer information summary unless it is presented in its entirety and is regularly updated. However, an author would be permitted to write a sentence such as “NCI’s PDQ cancer information summary about breast cancer prevention states the risks succinctly: [include excerpt from the summary].”
The preferred citation for this PDQ summary is:
PDQ® Adult Treatment Editorial Board. PDQ Breast Cancer Treatment. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/types/breast/hp/breast-treatment-pdq. Accessed <MM/DD/YYYY>. [PMID: 26389406]
Images in this summary are used with permission of the author(s), artist, and/or publisher for use within the PDQ summaries only. Permission to use images outside the context of PDQ information must be obtained from the owner(s) and cannot be granted by the National Cancer Institute. Information about using the illustrations in this summary, along with many other cancer-related images, is available in Visuals Online, a collection of over 2,000 scientific images.

Disclaimer

Based on the strength of the available evidence, treatment options may be described as either “standard” or “under clinical evaluation.” These classifications should not be used as a basis for insurance reimbursement determinations. More information on insurance coverage is available on Cancer.gov on the Managing Cancer Care page.

Contact Us

More information about contacting us or receiving help with the Cancer.gov website can be found on our Contact Us for Help page. Questions can also be submitted to Cancer.gov through the website’s Email Us.
  • Updated: March 15, 2019
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