Adjuvant Therapy of Primary Breast Cancer VI (Recent Results in Cancer Research)

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Adjuvant chemotherapy [ 9 , 20 ]. Chemotherapy has been demonstrated to provide survival benefit in premenopausal and postmenopausal women up to the age of 70 years and in most tumor subsets, except for small node-negative tumors less than 1 cm in diameter [ 9 , 12 ]. Such data call into question the optimal length of treatment of the AC regimen. Future trials are needed to define the optimal use of adjuvant anthracycline-based regimens. While waiting for results from such studies, the decision to use an anthracycline-based adjuvant therapy, and the type of such therapy, should be made on individual patients taking into consideration the potential survival benefits versus toxicity risks.

As anthracyclines and taxanes paclitaxel and docetaxel are the most active cytotoxic treatments available for advanced breast cancer, the evaluation of these agents in the adjuvant setting was logical [ 25 ]. Several trials have assessed the efficacy and safety of the addition of a taxane to standard anthracycline adjuvant chemotherapy in node-positive breast cancer [ 26 - 29 ]. A combination and B sequential administration.

Prospective phase III adjuvant trials with docetaxel, either in combination or in sequential administration to the anthracycline, are ongoing.

Acknowledgments

Whereas, adjuvant studies with paclitaxel are evaluating the combination in a sequential strategy [ 30 ]. There remains a possibility that paclitaxel provides some survival advantage to hormone-unresponsive patients, but the study design does not allow a firm conclusion because the potential advantage might be related simply to a longer exposure to chemotherapy. Patients were stratified according to number of positive axillary nodes, tamoxifen administration, and type of surgery. To date, no difference with regard to steroid hormone-receptor status has emerged.

Further follow-up of this trial is required, but the same problem on duration of treatment remains. The use of taxanes in node-negative breast cancer should be restricted to clinical trials as there are no data available yet to support the use of taxanes outside clinical trials.

There is no convincing evidence yet that high-dose chemotherapy with peripheral stem cell support is superior to standard therapy in the adjuvant setting [ 9 , 12 , 22 , 38 - 42 ]. Randomized trials are continuing to evaluate the value of high-dose chemotherapy, but it should not be offered outside of clinical trials.

Although at present there are no convincing data to justify the use of biological factors in selecting specific adjuvant chemotherapy, the predictive roles of p53 mutations and HER-2 overexpression are being explored in prospective studies. Additionally, the role of high-dose chemotherapy in the adjuvant setting, the definition of the contribution offered by the taxanes, and the integration of novel agents i. Planned, ongoing, and completed selected adjuvant studies comparing sequential to combination chemotherapy.

The Breast Cancer International Research Group BCIRG study will randomize patients to four cycles of AC followed by four cycles of docetaxel, or to four cycles of AC followed by four cycles of docetaxel plus trastuzumab for 1 year, or an intriguing triple regimen of docetaxel plus platinum salts plus trastuzumab [ 44 , 45 ].

Concerns on the toxicity associated with the use of adjuvant chemotherapy are reasonable. Most acute side effects i. Longer-term side effects with hormonal therapy small increase in risk of second malignancies, thromboembolism , chemotherapy i. At the cumulative doses utilized in standard anthracycline adjuvant programs in patients with no preexisting heart disease, excessive cardiac toxicity seems to be restricted [ 9 , 12 ].

Further studies are being conducted on these specific patient populations. Gallen Conference focused on adjuvant therapy for primary breast cancer; however, neoadjuvant therapy provides several advantages, namely it allows for in vivo tumor response to new anticancer agent assessments; reduces the likelihood of drug resistance as it allows a switch to non-cross-resistant regimens; takes advantage of the less favorable growth kinetics for micrometastases, and may increase the rate of breast conservation and achieve nodal downstaging [ 46 - 50 ].

In the past, randomized neoadjuvant studies produced inconclusive results, with some showing disease-free survival benefits at 5 years and others showing no difference versus adjuvant therapy [ 47 , 50 - 53 ]. Since then, however, biological determinants have been introduced and promise to enhance our understanding of particular characteristics of an individual tumor and best treatment options. It may be that neoadjuvant therapy will prove of interest in terms of survival for younger endocrine-unresponsive patients as an early start of chemotherapy seems to play a role only for this subset of patients [ 54 ].

The correlation between p53 and HER-2 expression as possible predictors of response to neoadjuvant chemotherapy is under investigation [ 55 ]. The NSABP B study showed significantly better disease-free and overall survival among patients achieving a pathological complete response [ 9 ]. Phase II neoadjuvant trials with the taxanes have produced encouraging results, which has prompted further evaluation in the phase III setting [ 56 - 62 ].

All patients received 5 years tamoxifen treatment. This study has recently closed, with 2, patients enrolled. The results from this study will help define the role of docetaxel in the neoadjuvant setting.

Studies will also need to address the issue of whether the inclusion of an anthracycline is essential in neoadjuvant regimens. With the establishment of adjuvant systemic therapy, the role of locoregional therapy has changed and moved toward less aggressive surgery combined with radiotherapy [ 63 ]. Randomized trials showed mastectomy, plus radiotherapy produced similar results to extensive radical mastectomy and the role of postoperative irradiation in breast-conserving therapy has been confirmed [ 63 , 64 ]. Analyses have shown that radiotherapy can significantly reduce the locoregional recurrence rate but does not significantly improve the long-term survival of the patient [ 63 , 65 , 66 ].

More recent studies in patients with well-defined pathologically staged high-risk breast cancer have demonstrated a clinically relevant improvement in survival in some patients receiving radiotherapy and systemic therapy [ 63 ]. From these studies, it was concluded that improving locoregional tumor control could improve overall survival rates and that radiotherapy was an important part of the multimodality approach to the treatment of high-risk breast cancer [ 9 , 12 , 63 ].

However, radiotherapy should not be delivered concurrently with anthracycline chemotherapy [ 9 , 12 ]. It is uncertain whether women with only one to three positive lymph nodes would benefit from postmastectomy radiotherapy. This is being addressed in ongoing randomized trials. Breast cancer mortality rates are decreasing, and this is due in part to the progress made in the adjuvant treatment of primary breast cancer and efficient earlier screening programs [ 1 ].

It is hoped that the novel predictive and prognostic factors will be confirmed, through the randomized trials, as reliable and accurate factors for predicting patient outcomes or response to specific treatments. These, together with currently established factors, will enhance the ability to customize patient treatments. Prospective adjuvant tamoxifen trials will provide insight to the value of continuing treatment beyond 5 years, of combined hormonal therapy, and of the benefits of SERMs and aromatase inhibitors.

The jury is still out on the role of tamoxifen as prevention for breast cancer. Neither this study, nor the Multiple Outcomes of Raloxifene Evaluation study comparing raloxifene to placebo established a reduction in breast cancer mortality. The Royal Marsden trial and the Italian trial demonstrated no effect of tamoxifen on the early incidence of breast cancer [ 67 ]. The International Breast Cancer Intervention Study IBIS trial enrolled 7, women with an increased risk of breast cancer; this study is now closed and an interim analysis is expected this year.

This may shed light on the role of tamoxifen in a preventative role. Additional studies are also under way: Long follow-ups are needed on these trials in order to demonstrate a clinical benefit or reduction in breast cancer mortality. The use of vaccines as an adjuvant therapy for breast cancer is in the early stage of evaluation [ 68 ].

As our knowledge on breast tumor cellular biology improves, potential targets for antigen-specific immunotherapy might have an important role to play in the management of this disease. With our increasing options for early treatment of breast cancer, we should achieve enhanced cure rates in primary breast cancer in the near future while avoiding overtreatment.

The editors gratefully acknowledge an unrestricted educational grant from Aventis Oncology. User Name Password Sign In. Adjuvant Therapy of Primary Breast Cancer: Gallen, February Matti S. Accepted July 13, Previous Section Next Section. In this window In a new window. Best Type of Endocrine Treatment and Duration of Endocrine Treatment The value of endocrine therapy was confirmed in the overview. Ovarian Ablation and Combined Treatments In the absence of chemotherapy, trials with ovarian ablation resulted in a reduction in recurrence by an absolute value of Adjuvant Hormonal Treatment Options in Development The combination of hormonal therapies is being evaluated, especially in studies involving selective estrogen-receptor modulators SERMs and aromatase inhibitors.

The Use of Taxanes and Anthracyclines as Adjuvant Chemotherapy As anthracyclines and taxanes paclitaxel and docetaxel are the most active cytotoxic treatments available for advanced breast cancer, the evaluation of these agents in the adjuvant setting was logical [ 25 ]. The Role of High-Dose Adjuvant Chemotherapy There is no convincing evidence yet that high-dose chemotherapy with peripheral stem cell support is superior to standard therapy in the adjuvant setting [ 9 , 12 , 22 , 38 - 42 ].

Side Effects and Quality of Life: The Impact on the Choice of Adjuvant Therapy Concerns on the toxicity associated with the use of adjuvant chemotherapy are reasonable. Cancer Incidence, Mortality and Prevalence Worldwide estimates. Accessed July 18, Lancet ; The evolution of paradigms for the management of breast cancer: Cancer Res ; Systemic chemotherapy as an adjuvant to surgery in the treatment of breast cancer. Cancer ; CrossRef Medline Google Scholar. Systemic treatment of early breast cancer by hormonal, cytotoxic or immune therapy. Tamoxifen for early breast cancer: Malignant tumors of the breast.

Cancer Principles and Practice of Oncology 5th ed. J Natl Cancer Inst ; Features that predict responsiveness to chemotherapy and endocrine therapies. The Breast ; 10 suppl 1: Therapeutic Advances in Breast Cancer. European Breast Cancer Conference Dissemination risk index based on plasminogen activator system components in primary breast cancer. J Clin Oncol ; A comparison of two doses of tamoxifen Nolvadex in postmenopausal women with advanced breast cancer: Br J Cancer ; Best types of endocrine treatments. Five versus more than five years tamoxifen therapy for breast cancer patients with negative lymph nodes and estrogen receptor-positive tumors.

Ovarian ablation in early breast cancer: Is chemotherapy alone adequate for young women with oestrogen-receptorpositive breast cancer? Effects of radiotherapy and surgery in early breast cancer. An overview of the randomized trials. N Engl J Med ; Burdens and benefits of adjuvant cyclophosphamide, methotrexate, and fluorouracil and tamoxifen for elderly patients with breast cancer: Best types of adjuvant chemotherapy.

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Polychemotherapy for early breast cancer: Best timing and duration of adjuvant chemotherapy. The use of anthracyclines and taxanes in the adjuvant therapy of breast cancer. Proc Am Soc Clin Oncol ; Taxane-based three-drug combination in metastatic and adjuvant treatment of breast cancer. Semin Oncol ; 25 suppl Combination versus sequential doxorubicin and docetaxel as primary chemotherapy for breast cancer: Role of paclitaxel in adjuvant therapy of operable breast cancer: Nabholtz JM, Riva A. The Oncologist ; 6 suppl 3: In testicular cancer , adjuvant either radiotherapy or chemotherapy may be used following orchidectomy.

Previously, mainly radiotherapy was used, as a full course of cytotoxic chemotherapy produced far more side effects then a course of external beam radiotherapy EBRT. Adjuvant therapy is particularly effective in certain types of cancer, including colorectal carcinoma , lung cancer , and medulloblastoma. Prophylactic cranial irradiation for acute lymphoblastic leukemia ALL is technically adjuvant, and most experts agree that cranial irradiation decreases risk of central nervous system CNS relapse in ALL and possibly acute myeloid leukemia AML , but it can cause severe side effects, and adjuvant intrathecal methotrexate and hydrocortisone may be just as effective as cranial irradiation, without severe late effects , such as developmental disability , dementia , and increased risk for second malignancy.

Dose-dense chemotherapy DDC has recently emerged as an effective method of adjuvant chemotherapy administration. DDC uses the Gompertz curve to explain tumor cell growth after initial surgery removes most of the tumor mass. Cancer cells that are left over after a surgery are typically rapidly dividing cells, leaving them the most vulnerable to chemotherapy. Standard chemotherapy regimens are usually administered every 3 weeks to allow normal cells time to recover.

This practice has led scientists to the hypothesis that the recurrence of cancer after surgery and chemo may be due to the rapidly diving cells outpacing the rate of chemotherapy administration. DDC tries to circumvent this issue by giving chemotherapy every 2 weeks. To lessen the side effects of chemotherapy that can be exacerbated with more closely administered chemotherapy treatments, growth factors are typically given in conjunction with DDC to restore white blood cell counts.

The role of adjuvant therapy in malignant melanoma is and has been hotly debated by oncologists.

Adjuvant therapy

In a multicenter study reported improved long-term and disease-free survival in melanoma patients using interferon alpha 2b as an adjuvant therapy. Thus, later that year the U. Food and Drug Administration FDA approved interferon alpha 2b for melanoma patients who are currently free of disease, to reduce the risk of recurrence. Since then, however, some doctors [ who? Those claims have not been validated by scientific research. Adjuvant chemotherapy has been used in malignant melanoma, but there is little hard evidence to use chemotherapy in the adjuvant setting. However, melanoma is not a chemotherapy-resistant malignancy.

Multiple studies have shown that adjuvant radiotherapy improves local recurrence rates in high-risk melanoma patients. The studies include at least two M. Anderson cancer center studies. However, none of the studies showed that adjuvant radiotherapy had a statistically significant survival benefit. A number of studies are currently underway to determine whether immunomodulatory agents which have proven effective in the metastatic setting are of benefit as adjuvant therapy for patients with resected stage 3 or 4 disease.

Adjuvant chemotherapy is effective in preventing the outgrowth of micrometastatic disease from colorectal cancer that has been removed surgically. Studies have shown that fluorouracil is an effective adjuvant chemotherapy among patients with microsatellite stability or low-frequency microsatellite instability , but not in patients with high-frequency microsatellite instability.

Exocrine pancreatic cancer has one of the lowest 5-year survival rates out of all cancers. A series of studies has established that 6 months of chemotherapy with either gemcitabine or fluorouracil, as compared with observation, improves overall survival. Newer trials incorporating immune checkpoint inhibitors such as the inhibitors to programmed death 1 PD-1 and the PD-1 ligand PD-L1 are under way.

The toxicity resulting from adjuvant chemotherapy was believed to be manageable. Neoadjuvant platinum-based chemotherapy has been demonstrated to improve overall survival in advanced bladder cancer , but there exists some controversy in the administration. While it may shrink tumors in some patients, others may not respond to the treatment at all. It has been demonstrated that a delay in surgery of greater than 12 weeks from the time of diagnosis can decrease overall survival.

Thus, the timing for neoadjuvants becomes critical, as a course of neoadjuvant therapy could delay a cystectomy and allow the tumor to grow and further metastasize. It has been known for at least 30 years that adjuvant chemotherapy increases the relapse-free survival rate for patients with breast cancer [22] In after a national consensus conference, a US National Institute of Health panel concluded: However, ethical concerns have been raised about the magnitude of benefit of this therapy since it involves further treatment of patients without knowing the possibility of relapse.

Bernard Fisher, among the first to conduct a clinical trial evaluating the efficacy of adjuvant therapy on patients with breast cancer, described it as an "value judgement" in which the potential benefits must be evaluated against the toxicity and cost of treatment and other potential side effects. Giving two or more chemotheraputic agents at once may decrease the chances of recurrence of the cancer, and increase overall survival in patients with breast cancer. Commonly used combination chemotherapy regimines used include:.

An additional surgical focus for young women with early-stage cancers is on the conservation of the contralateral ovary for the preservation of fertility. Most cases of ovarian cancers are detected at the advanced stages, when the survival is greatly reduced. In early stage cervical cancers, research suggests that adjuvant platinum-based chemotherapy after chemo-radiation may improve survival.

For advanced cervical cancers, further research is needed to determine the efficacy, toxicity and effect on the quality of life of adjuvant chemotherapy.

Adjuvant therapy - Wikipedia

Since most early-stage endometrial cancer cases are diagnosed early and are typically very curable with surgery, adjuvant therapy is only given after surveillance and histological factors determine that a patient is at high risk for recurrence. Adjuvant pelvic radiation therapy has received scrutiny for its use in women under 60, as studies have indicated decreased survival and increased risk of second malignancies following treatment.

In advanced-stage endometrial cancer, adjuvant therapy is typically radiation, chemotherapy, or a combination of the two. For seminoma, the three standard options are: For non-seminoma, the options include: As is the case for all reproductive cancers, a degree of caution is taken when deciding to use adjuvant therapy to treat early stage testicular cancer.

Depending on what form of treatment is used, adjuvant therapy can have side effects , like all therapy for neoplasms. Chemotherapy frequently causes vomiting , nausea , alopecia , mucositis , myelosuppression particularly neutropenia , sometimes resulting in septicaemia. Some chemotheraputic agents can cause acute myeloid leukaemia , in particular the alkylating agents.

Rarely, this risk may outweigh the risk of recurrence of the primary tumor. Depending on the agents used, side effects such as chemotherapy-induced peripheral neuropathy , leukoencephalopathy , bladder damage, constipation or diarrhea , hemorrhage , or post-chemotherapy cognitive impairment. For instance, radiotherapy to the brain can cause memory loss , headache , alopecia , and radiation necrosis of the brain.

If the abdomen or spine is irradiated, nausea, vomiting, diarrhea, and dysphagia can occur. If the pelvis is irradiated, prostatitis, proctitis , dysuria , metritis , diarrhea, and abdominal pain can occur. Adjuvant hormonal therapy for prostate cancer may cause cardiovascular disease, and other, possibly severe, side effects.

From Wikipedia, the free encyclopedia. For adjuvant substances, see adjuvant. This article needs more medical references for verification or relies too heavily on primary sources. Please review the contents of the article and add the appropriate references if you can. Unsourced or poorly sourced material may be challenged and removed. Basic and Clinical Research.

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