Delay in Radiation Therapy Increases Risk of Breast Cancer Recurrence

Among older women who undergo breast-conserving surgery (lumpectomy) for early breast cancer, a longer interval between surgery and the start of radiation therapy increases the risk of local cancer recurrence. These results were published in the British Medical Journal.

Surgery for early-stage breast cancer involves either a mastectomy or a lumpectomy. A mastectomy involves removal of the entire breast, whereas a lumpectomy involves removal of the cancer and some surrounding tissue.? Because a lumpectomy alone is associated with a higher rate of cancer recurrence than mastectomy, patients who elect to have a lumpectomy are also treated with radiation therapy. The combination of lumpectomy and radiation is referred to as breast-conserving therapy. Breast-conserving therapy and mastectomy produce similar rates of long-term survival.

Among women who undergo breast-conserving therapy, prompt treatment with radiation therapy after surgery may result in better outcomes than delayed radiation therapy. To explore this issue, researchers evaluated information from a large U.S. database that links cancer registry data with Medicare claims data. Information was available for more than 18,000 women over the age of 65 who had undergone breast-conserving therapy for Stage 0-II breast cancer. The study was restricted to women who did not receive chemotherapy.

The primary outcome of interest was the rate of local cancer recurrence (cancer recurrence within the breast).

The median time from surgery to start of radiation therapy was 34 days. Thirty percent of women started radiation therapy more than six weeks after surgery.

Longer intervals between surgery and the start of radiation therapy were linked with an increased risk of local cancer recurrence. For example, women who started radiation therapy more than six weeks after surgery were 19% more likely to experience local cancer recurrence than women who had a shorter interval between surgery and radiation.Women were more likely to have a longer interval between surgery and the start of radiation therapy if they had positive lymph nodes, other health conditions, a history of low income, or were of Hispanic ethnicity or non-White race. Longer intervals were also more common in regions of the United States that had higher rates of breast-conserving therapy, suggesting that busy treatment facilities may have longer wait times.

These results suggest that starting radiation therapy as soon as possible after lumpectomy may reduce the risk of local cancer recurrence.

Reference: Punglia RS, Saito AM, Neville BA, Earle CC, Weeks JC. Impact of interval from breast conserving surgery to radiotherapy on local recurrence in older women with breast cancer: retrospective cohort analysis. British Medical Journal [early online publication]. March 2, 2010.

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Single-dose Radiation in Early Breast Cancer

A single dose of radiotherapy delivered at the time of surgery may be an effective alternative to external beam radiation delivered over several weeks among selected patients with early breast cancer. Findings of this international Phase III trial were published in The Lancet.

Treatment for early-stage breast cancer often involves breast conserving surgery (lumpectomy), which may be followed by radiation therapy to decrease risk of recurrence. ?Two methods of delivering radiation include:

External beam radiation: High-energy rays are delivered to the breast from a machine outside the body over several weeks. Single dose intraoperative therapy: One dose of radiation is delivered at the time of surgery.

To compare the outcomes of a single dose of targeted radiotherapy delivered at the time of surgery with those of external beam radiation delivered over several weeks, researchers evaluated the two approaches in more than 2,000 women with early breast cancer. Participants were aged 45 or older. Approximately half the patients received a single dose of radiotherapy at the time of surgery, and approximately half received external beam radiation over several weeks. All women underwent breast-conserving surgery.

At four years outcomes of both approaches were similar: There were six local recurrences in the targeted radiation group compared with five in the external beam radiation group. As well, both groups experienced similar side effects and frequency of side effects.

It appears that among some patients with early breast cancer, a single dose of radiotherapy at the time of surgery may be an effective alternative to several weeks of external beam radiation therapy. The researchers caution, however, that these findings may not apply to all patients with early breast cancer, as this study evaluated only women who were 45 or older and considered appropriate candidates for breast-conserving surgery.? In addition, the follow-up remains too short to draw definitive conclusions. It will be important to see if there is any change in the results over time.

Reference: ?Vaidya JS, Joseph DJ, Tobias, JS, et al. Targeted intraoperative radiotherapy versus whole breast radiotherapy for breast cancer (TARGIT-A trial): an international, prospective, randomised, non-inferiority phase 3 trial. The Lancet [early online publication]. June 5, 2010.

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In Preclinical Studies, New Drug Enhances Radiation Treatment For Brain Cancer

Main Category: Cancer / Oncology
Also Included In: Neurology / Neuroscience;??Radiology / Nuclear Medicine
Article Date: 16 May 2013 - 1:00 PDT Current ratings for:
In Preclinical Studies, New Drug Enhances Radiation Treatment For Brain Cancer

A novel drug may help increase the effectiveness of radiation therapy for the most deadly form of brain cancer, report scientists at Virginia Commonwealth University Massey Cancer Center. In mouse models of human glioblastoma multiforme (GBM), the new drug helped significantly extend survival when used in combination with radiation therapy.

Recently published in the journal Clinical Cancer Research, the study provides the first preclinical evidence demonstrating that an ATM kinase inhibitor radiosensitizes gliomas. Gliomas are brain tumors that originate from glial cells, which provide support for nerve cells and help regulate the internal environment of the brain. ATM, or ataxia telangiectasia mutated, is an enzyme that helps repair DNA damage. The scientists used an experimental drug, KU-60019, to block the activation of ATM, which led to the enhanced destruction of the gliomas due to their reduced ability to repair the DNA damage caused by the radiation treatment. The new approach was particularly effective against gliomas that have a mutation in the p53 tumor suppressor gene, which accounts for approximately 30 percent of all glioma cases.

"Sadly, the average life expectancy of patients diagnosed with glioblastoma is just 12 to 15 months," says the study's lead researcher Kristoffer Valerie, Ph.D., co-leader of the Radiation Biology and Oncology research program and a professor in the Department of Radiation Oncology at VCU Massey Cancer Center. "By limiting the tumor's ability to combat DNA damage caused by treatments such as radiation, we are hopeful that we can enhance our ability to specifically target the glioma, prolong survival and reduce damage to surrounding brain tissue."

Currently, GBM is treated with surgery, followed by chemotherapy and radiation therapy. Potentially, ATM kinase inhibitors like the one used in this study could enhance the effectiveness of some other cancer treatments that kill tumor cells by damaging DNA. The scientists chose radiation therapy in this study since it is already standard care and can be delivered to brain tumors with extreme accuracy, minimizing damage to surrounding healthy tissue.

"If these findings hold up in early phase clinical trials, we expect patients with p53 mutant gliomas to respond well to this treatment while showing few side effects. Also, we anticipate that this same treatment strategy could be effective for other cancers that are treated with DNA-damaging chemotherapies," says Valerie. "We are encouraged by these early findings and will continue to move forward with our research. However, more studies are needed before we can proceed with testing this new therapy in humans."

This first, 'proof-of-principle' study is an important follow-up of a study published several years ago on KU-60019 by Valerie and his research team that demonstrated KU-60019's superior efficacy, specificity and potency on glioma cells as compared to a predecessor ATM inhibitor.

Valerie and his team are conducting additional studies examining the effects of KU-60019 and other ATM kinase inhibitors on gliomas, including studies that combine ATM kinase inhibitors with a type of drug known as a PARP inhibitor to increase the effectiveness of the treatment. PARP inhibitors block the action of poly ADP ribose polymerase (PARP), an enzyme that also aids in the repair of DNA damage. The researchers believe that combining an ATM kinase inhibitor with a PARP inhibitor may cause a condition referred to as "synthetic lethality," which arises when the functions of at least two interacting genes are simultaneously inhibited, which, in turn, leads to tumor cell death.

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our cancer / oncology section for the latest news on this subject. Valerie collaborated on this study with Sumitra Deb, Ph.D., a member of the Cancer Molecular Genetics research program at VCU Massey Cancer Center and professor in the Department of Biochemistry and Molecular Biology at VCU School of Medicine; Nitai D. Mukhopadhyay, M.Stat., Ph.D., a member of the Radiation Biology and Oncology research program at VCU Massey and assistant professor in the Department of Biostatistics at VCU School of Medicine; Laura Biddlestone-Thorpe, Muhammad Sajjad, Elizabeth Rosenberg, Jason M. Beckta, Nicholas C.K. Valerie, Mary Tokarz, Bret R. Adams, Alison F Wagner, Ashraf Khalil, Donna Gilfor and Sarah E. Golding, all from the Department of Radiation Oncology at VCU School of Medicine; David G. Temesi, Ph.D., Alan Lau, Ph.D., and Mark J. O'Connor, Ph.D., all from AstraZeneca; and Kevin S Choe, M.D., Ph.D., Luis F. Parada, Ph.D., and Sang Kyun Lim, Ph.D., all from the University of Texas Southwestern.

This study was supported by National Institutes of Health Grant R01NS064593 and National Cancer Institute Grants R21CA156995, T32CA113277, T32CA085159, T32CA085159 and F30CA171893. Additional support was provided by the American Brain Tumor Association and, in part, by funding from VCU Massey Cancer Center's NIH-NCI Cancer Center Support Grant P30 CA016059.

The full manuscript of this study is available online at: http://clincancerres.aacrjournals.org/content/early/2013/04/25/1078-0432.CCR-12-3408.abstract

Virginia Commonwealth University

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Lumpectomy without Radiation an Option for Some Older Breast Cancer Patients

Among women aged 70 or older with Stage I, estrogen receptor-positive breast cancer, treatment with lumpectomy and tamoxifen resulted in a higher rate of cancer recurrence but similar overall survival as treatment with lumpectomy, tamoxifen, and radiation therapy. These results, which will be presented at the 2010 annual meeting of the American Society of Clinical Oncology, suggest that some older women may be able to forego radiation therapy without adversely affecting survival.

Surgery for early-stage breast cancer typically involves either mastectomy or lumpectomy. A mastectomy involves removal of the entire breast, whereas a lumpectomy involves removal of the cancer and a portion of surrounding tissue.? Because a lumpectomy alone is associated with a higher rate of cancer recurrence than mastectomy, patients who elect to have a lumpectomy are generally also treated with radiation therapy. The combination of lumpectomy and radiation is called breast-conserving therapy. Studies have shown that breast-conserving therapy is associated with a lower risk of local cancer recurrence than lumpectomy alone.

Although the addition of radiation therapy to lumpectomy reduces the risk of local cancer recurrence, radiation therapy typically takes place over several weeks and requires a large commitment of time from the patient. This has prompted interest in whether there are certain groups of women with early breast cancer who can safely forego radiation therapy after lumpectomy.

The current study involved 636 women aged 70 or older with Stage I, estrogen receptor-positive breast cancer. After lumpectomy, women were assigned to additional treatment with tamoxifen alone or tamoxifen plus radiation therapy.

Women have now been followed for over 10 years.

The risk of cancer recurrence in the same breast was lower among women who received radiation therapy: a local cancer recurrence developed in 2% of women treated with tamoxifen and radiation therapy and 8% of women treated with tamoxifen alone.Breast cancer-specific and overall survival were similar in the two study groups: 10-year overall survival was 61% among women treated with tamoxifen and radiation therapy and 63% in women treated with tamoxifen alone.

These results suggest that among older women treated with lumpectomy and tamoxifen for Stage I, estrogen receptor-positive breast cancer, skipping radiation therapy increases the risk of local cancer recurrence but does not adversely affect overall survival.

Older women with early breast cancer may wish to talk with their doctor about the risks and benefits of all treatment options.

Reference: Hughes KS, Schnaper LA, Cirrincione C et al. Lumpectomy plus tamoxifen with or without irradiation in women age 70 or older with early breast cancer. To be presented at the 2010 annual meeting of the American Society of Clinical Oncology. June 4-8, 2010. Chicago, IL. Abstract 507.

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Additional Evidence That Post-Lumpectomy Radiation Improves Breast Cancer Outcomes

?In addition to reducing the risk of breast cancer recurrence, post-lumpectomy radiation therapy improves survival among women with early breast cancer. These results—from a combined analysis of 17 previous studies—were published in The Lancet.?????

Surgery for early-stage breast cancer may consist of mastectomy or lumpectomy. A?mastectomy?involves removal of the entire breast, whereas a?lumpectomy?involves removal of the cancer and some surrounding tissue. A lumpectomy is usually followed by radiation therapy in order to reduce the risk of cancer recurrence in or near the breast. The combination of lumpectomy and radiation therapy is referred to as breast-conserving therapy.???

Several previous studies have reported giving radiation therapy after lumpectomy results in a lower risk of breast cancer recurrence than lumpectomy alone. To further evaluate the benefits of post-lumpectomy radiation therapy, researchers conducted a combined analysis of 17 previous studies. These studies included more than 10,000 women with early-stage breast cancer.???

Post-lumpectomy radiation therapy reduced the 10-year risk of breast cancer recurrence from 35% to 19%. ?The 15-year risk of death from breast cancer was 25% among women who did not receive post-lumpectomy radiation therapy and 21% among women who did receive radiation therapy. ?For every four breast cancer recurrences that were prevented by radiation therapy by year 10, one breast cancer death was prevented by year 15.?Benefits of radiation therapy were seen in women with node-negative breast cancer as well as women with node-positive breast cancer.?

These results provide additional evidence that giving radiation therapy after a lumpectomy substantially reduces the risk of cancer recurrence and also reduces the risk of death from breast cancer.?????

Reference: Early Breast Cancer Trialists’ Collaborative Group. Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: meta-analysis of individual patient data for 10,801 women in 17 randomised trials. Lancet. Early online publication October 20, 2011.?

Posted October 27, 2011?

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Screening Radiation Exposure May Increase Breast Cancer Risk in Some BRCA Mutation Carriers

Radiation exposure from x-rays, mammograms, and other diagnostic tests prior to age 30 may increase the risk of breast cancer in women who carry BRCA1 or BRCA2 mutations, according to the results of a large, retrospective cohort study published in the British Medical Journal. ?

Inherited mutations in two genes—BRCA1 and BRCA2—have been found to greatly increase the lifetime risk of developing breast and ovarian cancer. Mutations in these genes can be passed down through either the mother’s or the father’s side of the family.?

A mammogram is an X-ray of the breast. Screening mammography is performed in a woman without breast symptoms in order to detect breast cancer at an early stage when it is most easily treated. Currently, mammography is the most reliable tool for screening the general population for breast cancer and may even reduce the risk of death from breast cancer (due to early detection). Mammograms are most often used in women over the age of 40; however, women who carry BRCA mutations are considered high-risk and may benefit from earlier and more frequent screening. This earlier screening can come with the added risk of increased radiation exposure—and exposure to ionizing radiation, especially when it occurs at an early age, is an established risk factor for breast cancer.? ?

To examine the relationship between radiation exposure and breast cancer risk among BRCA1/2 mutation carriers, researchers from Europe followed nearly 2,000 women over age 18 with a BRCA1 or BRCA2 mutation. The women reported their history of procedures—such as x-rays or mammograms—that involved radiation to the chest or shoulders. The researchers then used this information to estimate the cumulative dose of radiation to the breast for each woman and compared this against confirmed breast cancer diagnoses among the women. ?

When compared with no exposure, any exposure to chest radiation prior to age 30 was associated with almost double the risk of breast cancer in BRCA1/2 mutation carriers. Exposure prior to age 20 was associated with a 62 percent increased risk. Women who received the highest doses or radiation prior to age 30 had almost four times the increased risk. In contrast, there was no evidence of an increased risk of breast cancer associated with exposure after age 30. ?

The researchers concluded that exposure to diagnostic radiation before age 30 among carriers of BRCA1/2 mutations was associated with an increased risk of breast cancer. What’s more—the increased risk of breast cancer was observed at radiation doses considerably lower than those associated with an increased risk among other populations. ?

Because women with BRCA1/2 mutations have an increased risk of developing breast cancer, some guidelines recommend earlier screening; however, the results of this study may indicate that BRCA1/2 carriers under age 30 might benefit from surveillance that uses non-ionizing radiation imaging, such as magnetic resonance imaging (MRI).?

Reference:?

Pijpe A, Andrieu N, Easton DF, et al. Exposure to diagnostic radiation and risk of breast cancer among carriers of BRCA1/2 mutations: retrospective cohort study (GENE-RAD-RISK). British Medical Journal. 2012; 2012;345:e5660?

Posted October 2, 2012

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