Why Does Promising Anti-Cancer Therapy Suddenly Stop Working?

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Main Category: Cancer / Oncology
Article Date: 24 Jun 2013 - 9:00 PDT Current ratings for:
Why Does Promising Anti-Cancer Therapy Suddenly Stop Working?

Why does anti-cancer therapy stop working at a specific stage? Scientists in Israel and the USA believe they have made a breakthrough in understanding why a hopeful anti-cancer therapy fails to destroy tumor cells successfully.

The researchers, whose study is published in PNAS (Proceedings of the National Academy of Sciences), believe their findings may lead to new approaches in overcoming this cul-de-sac.

Suppressing the mTOR (mammalian target Of Rapamycin) protein has been extremely challenging for oncologists.

mTOR plays a key role in regulating vital cell growth processes - it is a bit like a communications command center, receiving external signals from hormones, growth factors and proteins. It then sends out "on" or "off" signals for the cell to grow and divide, seek nutrition, or use that nutrition. mTOR is strongly activated in several solid cancers.

While drugs have been shown to suppress mTOR and have been successful in causing the death of cancer cells in the outer layers of malignant tumors, in clinical trials they have failed in destroying the core of those tumors.

Hypoxia (lack of oxygen) is an almost-universal characteristic of solid tumors that can affect how tumors respond to therapies. Scientists know that the condition of hypoxia affects the behavior of mTOR signaling, but nobody knew what the mechanism was.

Prof. Emeritus Raphael D. Levine, from the Institute of Chemistry at the Hebrew University of Jerusalem, Israel, and scientists from the David Geffen School of Medicine at UCLA and the California Institute of Technology set out to determine what role hypoxia plays on mTOR signaling in model brain cancer systems and whether this could explain why promising mTOR drugs fail.

They used a new microchip technology to measure the mTOR protein-signaling network in cancer cells. They also used a new set of theoretical tools derived from the physical sciences to interpret the results. This dual approach simplified an otherwise extremely complex biological system.

The mTOR biochemical pathway is a complex one

The investigators found that at a specific level of hypoxia, which is typical in solid tumors, the mTOR signaling network switches between two sets of properties. At exactly the moment when the switching over takes places, the theoretical models predicted that mTOR would not respond to mTOR-inhibiting medications.

According to the combined experiment finding, the researchers believe that the switching over might be a kind of phase transition, something not observed before in biological systems.

This phase transition happened very suddenly, and cells being studied stopped responding like they had done before. The authors wrote "In the case of the tumor, the 'drugging' of the mTOR ceased, meaning that the tumor was no longer inhibited."

These results: explain why promising mTOR-inhibiting drugs stop working at a specific stage"indicate that certain complex biological behaviors, which often confound scientists who are seeking to find effective therapies for human diseases, may be understood by the effective application of experimental and theoretical tools derived from the physical sciences."Levine wrote in the PNAS Abstract:

"We find a hypoxia-induced switch within a mammalian target of rapamycin (mTOR) signaling network. At the switching point, mTOR is predicted, and then shown by experiment, to be unresponsive to inhibition. These results may help explain the undistinguished performance of mTOR inhibitors in certain clinical trials."

In an animal study, scientists from the University of California San Diego, La Jolla, found that mTOR-inhibitors may have adverse effects on heart function in patients with ongoing heart problems.

Written by Christian Nordqvist
Copyright: Medical News Today
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posted by Greg Pawelski on 24 Jun 2013 at 12:17 pm

One of the themes at the 103rd Annual American Association of Cancer Research was the growing recognition that human tumors exist as microenvironments and not isolated single cells. The tumor microenvironment is characterized by regions of fluctuating hypoxia, low pH, and nutrient deprivation. Each of these microenvironment factors has been shown to cause severe disturbance in cell metabolism and physiology.

By examining drug-induced cell death events in native-state 3D (three dimensional) microclusters, the functional profiling platform has the unique capacity to capture stromal, cytokines (chemokines), macrophages, lymphocytes, vascular and inflammatory cell interactions with tumor cells, known to be crucial for clinical response prediction.

The microclusters recapitulate the human tumor environment, while the "3D" advancement recreates the extracellular matrix (metalloproteinases). The platform studies cancer response to drugs within this microenvironment, enabling it to provide clinically relevant predictions to cancer patients. It is this capacity to study human tumor microenvironments that distinguishes it from other platforms in the field.

Tumors are very complex organisms. Ignoring this complexity, most studies of human cancer in culture have focused upon individual tumor cells that have been removed from their complex microenvironment.

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Cancer Pain Eased By Therapy That Heats And Destroys Bone Tumors

Main Category: Cancer / Oncology
Also Included In: Pain / Anesthetics;??MRI / PET / Ultrasound
Article Date: 04 Jun 2013 - 1:00 PDT Current ratings for:
Cancer Pain Eased By Therapy That Heats And Destroys Bone Tumors

Patients with cancer that has spread to their bones are often treated with radiation therapy to reduce pain. But if that treatment doesn't work, or can't be used again, a second, effective option now exists. Results of a clinical trial on the new therapy, presented by a researcher at Jefferson's Kimmel Cancer Center, was presented at the annual meeting of the American Society of Clinical Oncology (ASCO).

Mark Hurwitz, MD, Director of Thermal Oncology for the Department of Radiation Oncology at Thomas Jefferson University and Hospital reported that the treatment, magnetic resonance image-guided focused ultrasound (MRIgFU) ablation therapy, significantly reduced pain in 67 percent of patients who received the treatment. The device, known as ExAblate, uses numerous small ultrasound beams designed to converge on a tumor within bone, heat it and destroy it.

"Pain is a common, often debilitating symptom of the spread of cancer to bones. We are pleased to now have a second therapy that can improve a patient's enjoyment of life," says Dr. Hurwitz, who led the clinical trial. A number of cancers spread to bones, and a substantial proportion of patients live for years with these metastases, which can have a profound impact on a patient's quality of life, he adds.

The findings of the trial led to approval of ExAblate last October by the U.S. Food and Drug Administration as second-line therapy for palliation of painful metastatic bone tumors. The first-line therapy is typically radiotherapy.

"The response to ExAblate was as good as radiotherapy, which was notable because it is very unusual to see a second-line treatment with a response rate that is as high as first-line therapy," Dr. Hurwitz says.

He added that use of ExAblate offers several advantages compared to other ablative therapies. "It is non-invasive and provides more detailed anatomic information so that we can visualize the complete beam path to make sure that critical structures such as vessels and nerves are not in the way," Dr. Hurwitz says. "We are also able to monitor the temperature in the tumor as well as in nearby normal tissues so that we do not inadvertently heat normal organs and tissues."

ExAblate has also been approved for treatment of uterine fibroids.

The study led by Dr. Hurwitz is a multicenter, randomized and placebo-controlled phase three clinical trial. The 142 patients enrolled could either not undergo, or had not responded to, radiation treatment.

Three months after ExAblate therapy, 67 percent of treated patients reported significant improvement in pain, compared to 21 percent in the placebo arm. They typically rated their pain as "much improved" or "very much improved," Dr. Hurwitz says. A quality of life assessment also measured significant improvement.

"The treatment is given just once, and a response occurs within days," he says. "There are a lot of patients who could potentially benefit from MR guided focused ultrasound."

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. The clinical trial was sponsored by Insightec Ltd., who developed ExAblate.
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'Cancer Pain Eased By Therapy That Heats And Destroys Bone Tumors'

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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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Additional Research on Menopausal Hormone Therapy and Breast Cancer

A recent study of menopausal hormone therapy and risk of breast cancer reported that risk may vary by body weight and the type of hormone therapy. These results were published in Cancer Epidemiology, Biomarkers, & Prevention.

As women reach menopause and beyond, more than 80% will experience symptoms such as hot flashes, night sweats, sleep disturbance, and vaginal dryness. Estrogen, with or without progestin, is an effective treatment for many of these symptoms. Over the last several years, however, studies have raised important concerns about the health effects of menopausal hormone therapy.

Use of estrogen plus progestin has been linked with an increased risk of heart disease, breast cancer, stroke, and blood clots and a decreased risk of fractures and colorectal cancer. Use of estrogen alone, which is generally reserved for women who have had a hysterectomy, has been linked with an increased risk of strokes and a decreased risk of fractures.

Although it is now well established that menopausal hormone therapy with estrogen plus progestin increases the risk of breast cancer, researchers continue to explore the question of which subgroups of women are at greatest risk. This information would help personalize messages about the risks and benefits of hormone therapy.

The current study evaluated information from the California Teachers Study. Of the more than 56,000 perimenopausal or postmenopausal women in the study, 2,857 developed invasive breast cancer during 10 years of follow-up.

Compared with women who had never used hormone therapy, women who had used estrogen alone for 15 years or longer had a 19% increased risk of breast cancer (A 19% increase in risk means that if a woman has a 5% risk of getting breast cancer in the next 20 years, the risk goes up to 6%.). Women who had used estrogen plus progestin for 15 years or longer had an 83% increased risk of breast cancer (An 83% increase means that if a woman has a 5% risk over 20 years, the risk goes up to approximately 9%).For users of estrogen plus progestin, risk varied by the specific type of regimen used. Continuous regimens (progestin every day of the month) appeared to increase breast cancer risk to a greater extent than sequential regimens (progestin only some days of the month).The increased risk of breast cancer among users of hormone therapy was most apparent among thinner women.Use of hormone therapy increased the risk of cancers that were estrogen receptor-positive and progesterone receptor-positive.

These results provide additional evidence regarding the links between menopausal hormone therapy and risk of breast cancer. Women who are considering hormone therapy to manage menopausal symptoms are advised to talk with their doctor about the risks and benefits.

Reference: Saxena T, Lee E, Henderson K et al. Menopausal hormone therapy and subsequent risk of specific invasive breast cancer subtypes in the California Teachers Study. Cancer Epidemiology, Biomarkers, & Prevention [early online publication]. August 10, 2010.

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Molecular Profiling Timely For Tailoring Cancer Therapy

Main Category: Cancer / Oncology
Also Included In: Genetics
Article Date: 17 May 2013 - 0:00 PDT Current ratings for:
Molecular Profiling Timely For Tailoring Cancer Therapy

A clinical trial has shown that patients, and their physicians, are eager to jump into next-era cancer care - analysis of an individual's tumor to find and target genetic mutations that drive the cancer. Results of the study, CUSTOM, are being presented at the 2013 annual meeting of the American Society of Clinical Oncology* years before investigators thought they would be ready.

CUSTOM is the first completed prospective clinical trial that used genetic analysis alone to assign cancer treatment for patients with one of three different cancers.

"We expected it would take five years to enroll 600 patients into CUSTOM. But in less than two years, 668 patients were recruited," says the study's lead investigator, Giuseppe Giaccone, MD, PhD, associate director for clinical research at Georgetown Lombardi Comprehensive Cancer Center.

"This was a surprise to all of us, especially since patients with advanced cancer who already had biopsies needed to undergo an additional biopsy for the study. But we found patients and their doctors are quite interested in this type of personalized medicine. They know that the molecular profile of the tumor is important," says Giaconne, who is also director of clinical research for the MedStar Georgetown Cancer Network, a regional oncology affiliation between MedStar Health and Georgetown Lombardi.

CUSTOM has proved to be a model for more efficient clinical trials, he adds. It showed that patients want to participate in this kind of research, and that it is feasible to do extensive genetic testing on a tumor biopsy in a timely manner - in this case, taking only two weeks to complete. It also demonstrated that it is safe to take new biopsy from patients with advanced cancer to provide the tissue needed for the analysis.

One of the other endpoints of the study, however, was not achieved. Researchers discovered that, in many cases, they did not have enough patients with rare cancer mutations to provide an accurate statistical analysis of response to novel drugs, says Giaccone.

Giaccone led the clinical trial while at the National Cancer Institute where he was the Chief of the Medical Oncology Branch, before he joined Georgetown in January. Researchers at Oregon Health & Science University also participated.

CUSTOM enrolled patients diagnosed with advanced stage non-small cell lung cancer, small cell lung cancer or thymic cancer. Researchers used next-generation sequencing, which was novel at the time, to look at almost 200 genes. From this, patients were assigned to different treatment groups based on genetic mutations or amplification.

Results from the largest group - patients with non-small cell lung cancer - had either an EGFR or a KRAS mutation, and results showed that those with EGFR mutations had a very high response to the drug erlotinib. "This is nothing new; we essentially confirmed what was already known," Giaccone says. But they also discovered that patients with KRAS mutations did not benefit from the single agent investigational drug selumetinib, which is being studied for use in a number of cancers, including non-small cell lung cancer.

Results for the patients with small cell lung or thymic cancers were inconclusive, primarily because the investigated mutations were rare -not enough patients had specific mutations to adequately test response to therapy. "When we started the study, we didn't know how frequently the mutations occurred," Giaccone says. "Now we know that many mutations represent only 1 to 2 percent of patients and to do this right, you need to screen thousands of patients. That is only possible with a global study that involves, potentially, hundreds of institutions.

"The CUSTOM trial demonstrates both the feasibility of the approach for common mutations - that it is possible to have a real-time genetic analysis that guides treatment - as well as the difficulty of studying treatment for rare mutations," he says.

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. ASCO Annual Meeting: May 31-June 4, 2013 | McCormick Place | Chicago, Illinois

The Intramural Program of the National Cancer Institute funded the study. Giaccone reports having no personal financial interests related to the study.

Georgetown University Medical Center

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Updated Guidelines Address Hormonal Therapy for Breast Cancer

Among postmenopausal women with hormone receptor-positive breast cancer, use of an aromatase inhibitor at some point in the course of adjuvant (post-surgery) treatment results in a lower risk of cancer recurrence than use of tamoxifen only. Based on these results, updated guidelines from the American Society of Clinical Oncology recommend consideration of aromatase inhibitor therapy for this group of patients.[1]??

Each year roughly 200,000 U.S. women are diagnosed with breast cancer. Many of these breast cancers will be hormone receptor-positive, meaning that they are stimulated to grow by the circulating female hormones estrogen and/or progesterone.

Treatment of hormone receptor-positive breast cancer often involves hormonal therapies that suppress or block the action of estrogen. These therapies include tamoxifen as well as agents known as aromatase inhibitors. Tamoxifen acts by blocking estrogen receptors, whereas aromatase inhibitors suppress the production of estrogen in postmenopausal women. Aromatase inhibitors include ArimidexR (anastrozole), FemaraR (letrozole), and AromasinR (exemestane).

Several large trials comparing aromatase inhibitors to tamoxifen have established the efficacy of aromatase inhibitors for the treatment of hormone receptor-positive breast cancers among postmenopausal women. Whether aromatase inhibitors are used as initial hormonal therapy or sequentially with tamoxifen, use of an aromatase inhibitor at some point during the course of adjuvant treatment has been shown to reduce the risk of breast cancer recurrence compared with tamoxifen alone.

Based on these results, the American Society of Clinical Oncology recently updated its hormonal therapy guidelines.? As recommended in the latest guideline, the panel recommends that “postmenopausal women with hormone receptor-positive breast cancer consider incorporating [aromatase inhibitor] therapy at some point during adjuvant treatment, either as up-front therapy or as sequential treatment after tamoxifen. The optimal timing and duration of endocrine therapy treatment remain unresolved.”

Potential side effects of aromatase inhibitors that will need to be considered by the patient and her physician include bone loss and joint pain. Aromatase inhibitors also appear to be more likely than tamoxifen to cause increases in blood pressure and cholesterol levels.

Reference:

[1] Burstein HJ, Prestrud AA, Seidenfeld J et al. American Society of Clinical Oncology Clinical Practice Guidelines: Update on adjuvant endocrine therapy for women with hormone receptor-positive breast cancer. Journal of Clinical Oncology [early online publication]. July 12, 2010.

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Many Breast Cancer Patients Taking Adjuvant Hormonal Therapy Stop Treatment Early

Less than half of early-stage breast cancer patients with hormone-sensitive disease completed the full dose and schedule of their hormonal therapy treatment. These findings were recently published in the Journal of Clinical Oncology.[1]

The majority of breast cancers are hormone receptor-positive. These cancers are stimulated to grow by the circulating female hormones estrogen and/or progesterone. Treatment of hormone receptor-positive breast cancer often involves hormonal therapies that suppress or block the action of estrogen. These therapies include tamoxifen as well as agents known as aromatase inhibitors. Tamoxifen acts by blocking estrogen receptors, whereas aromatase inhibitors suppress the production of estrogen in postmenopausal women.?

Possible side effects of aromatase inhibitors include joint pain, decreased bone density, hot flashes, and vaginal dryness. Tamoxifen is associated with some side effects similar to symptoms of menopause, which include hot flashes, irregular menstrual periods and vaginal discharge or bleeding. Not all women will experience these symptoms. There is a small increase in the number of blood clots in individuals taking tamoxifen. In addition, tamoxifen appears to increase a woman’s risk of developing uterine cancer, though the risk is less than 1% over a 5-year course of treatment.?

Due to the duration of treatment with adjuvant hormonal therapy as well as possible side effects of treatment, patient adherence and continuation of therapy for the full duration can be challenging. According to the results of a study conducted in Ireland, many women who begin taking tamoxifen for the adjuvant treatment of breast cancer discontinue use (without switching to another hormonal therapy) before completing five years of treatment.[2] In this study, older and younger patients were more likely to discontinue treatment as well as patients with additional health problems. Results from another study indicated that noncompliance with tamoxifen is common and results in significantly increased risk of recurrence.[3] Medication adherence is very important in order to reduce risk of cancer recurrence or mortality. Researchers recently conducted a study in early-stage breast cancer patients receiving tamoxifen and/or an aromatase inhibitor in order to better understand adherence and continuation issues in this patient population.

In the current study, researchers evaluated pharmacy records of 8,769 Stage I-III hormone-sensitive breast cancer patients. Forty-three percent were undergoing hormonal therapy with tamoxifen, 26% with an aromatase inhibitor, and 30% with both tamoxifen and an aromatase inhibitor (sequentially). From the pharmacy records, hormonal therapy prescriptions and dates of refill were analyzed in order to determine rates of therapy discontinuation and adherence. The researchers were also able to analyze factors associated with suboptimal hormonal therapy dose or schedule from the pharmacy data. Of the 8,769 patients evaluated in this study, only 49% completed adjuvant hormonal therapy at the full dose and schedule. Factors associated with stopping treatment early included younger or older age as well as the presence of additional medical problems (comorbidites). Lumpectomy versus mastectomy was also associated with stopping treatment early. Factors associated with completing therapy included Asian race and being married. Treatment with chemotherapy and radiation in addition to hormonal therapy was also associated with completing hormonal therapy.?

These researchers concluded that “interventions to improve adherence and continuation of hormonal therapy are needed, especially for younger women.” This study confirms findings of other studies evaluating hormonal therapy adherence issues. Strategies to improve patient adherence to treatment schedules and doses are critical to improve recurrence rates, especially for oral therapy like adjuvant hormonal therapy. It is critical for breast cancer patients who are undergoing treatment with adjuvant hormonal therapy to understand the risks and benefits of treatments as well as to understand the risks of stopping treatment early.?

References:

[1] Hershman DL, Kushi LH, Shao T, et al. Early Discontinuation and Nonadherence to Adjuvant Hormonal Therapy in a Cohort of 8,769 Early-Stage Breast Cancer Patients. Journal of Clinical Oncology. [early online publication]. June 28, 2010.

[2] Barron TI, Connolly R, Bennett K, Feely J, Kennedy MJ. Early discontinuation of tamoxifen: a lesson for oncologists. Cancer [early online publication]. January 22, 2007.

[3] Ma AMT, Barone J, Wallis AE, et al. Noncompliance with adjuvant radiation, chemotherapy, or hormonal therapy in breast cancer patients. American Journal of Surgery. 2008;196:500-504.

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Higher Copayments May Limit Use of Breast Cancer Therapy

It appears that women with early breast cancer who are prescribed treatment with aromatase inhibitors (AIs) are more likely to discontinue or not follow through with this therapy if insurance copayments are high. These results were presented at the 2010 San Antonio Breast Cancer Symposium.

Treatment of hormone receptor-positive breast cancer often involves hormonal therapies that suppress or block the action of estrogen. These therapies include tamoxifen as well as agents known as aromatase inhibitors. Tamoxifen acts by blocking estrogen receptors, whereas aromatase inhibitors suppress the production of estrogen in postmenopausal women.

It’s not uncommon for women to fail to adhere to treatment with hormonal therapy. Previous studies have indicated that a woman’s age, the severity of side effects of hormonal therapy, and whether or not she believes the medicine is effective can influence her adherence to treatment. Little is known, however, about how the expense of these therapies may affect rates of adherence.

The impact of insurance copayments on adherence to AIs was evaluated in a study of 8,110 women aged 50 to 65 and 14,050 women aged 65 and older. The researchers investigated two different types of non-adherence: whether patients stopped using AIs entirely and didn’t get any refills or whether patients did not take AIs as prescribed (did not refill prescription on time or did not take AIs at least 80% of the time). Researchers categorized copayments as follows: less than $30, between $30 and $89.99, and $90 or more.

21.2% of the 8,110 patients aged 50 to 65 stopped taking AIs.Of the patients aged 50 to 65 who stayed on treatment during a two-year period, 10.3% did not take AIs as prescribed.Almost 25% of the 14,050 patients aged 65 and older stopped taking AIs.8.9% of patients aged 65 and older who continued taking AIs did not do so as prescribed. Women 65 years and older were more likely to discontinue AIs if their copayments were greater than $30.Women younger than 65 years became more likely to discontinue AIs when copayments were $90 or greater. It was also noted that when AIs were prescribed by a primary-care doctor, women were less likely to stay on treatment. This was also the case among women prescribed many other medications in addition to AIs.

These results indicate that higher prescription copayments limit the use of AIs, making patients more likely to either discontinue treatment or not take AIs as prescribed and that older women are more likely to be affected. Because AIs can be highly effective, the researchers suggest that “future public policy efforts should be directed towards reducing financial constraints as a means of increasing the complete use of these medications.”

Reference: Hershman DL, Neugut AI, Subar M, et al. Association between prescription co-payment amount and compliance with adjuvant aromatase inhibitor therapy in women with early stage breast cancer. Presented at the 33rd annual San Antonio Breast Cancer Symposium, December 8-12, 2010. Abstract S6-4.

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Breast-Conserving Therapy Effective in Young Women with Breast Cancer

Two studies presented at the 2011 Breast Cancer Symposium provide evidence that breast-conserving therapy (lumpectomy plus radiation therapy) is as effective as mastectomy for young women with early-stage breast cancer. ?

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. ?

Studies have indicated that mastectomy and breast-conserving therapy produce similar long-term survival among women with early-stage breast cancer. Some research has suggested, however, that young women may have a higher risk of breast cancer recurrence than older women after breast-conserving therapy. Concerns about recurrence risk may be contributing to the increasing use of mastectomy among young women.?

Two studies that will be presented at the 2011 Breast Cancer Symposium explore whether type of surgery affects outcomes among young women with breast cancer. The first study involved 628 women age 40 and younger who were treated for early-stage breast cancer at Massachusetts General Hospital.[1] ?

Risk of a local breast cancer recurrence (a recurrence in or near the breast) did not vary significantly by type of surgery. By five years, the risk of a local breast cancer recurrence was 4.6% among women treated with breast-conserving therapy and 8.5% among women treated with mastectomy. By ten years, the risk was 13.3% among women treated with breast-conserving therapy and 10.8% among women treated with mastectomy. ?

The second study collected information from a large national database about more than 14,000 breast cancer patients under the age of 40. [2] After accounting for patient and tumor characteristics, breast-conserving therapy and mastectomy produced similar overall survival. Ten-year overall survival was 83.5% among women treated with breast-conserving therapy and 83.6% among women treated with mastectomy.?

Together, these studies suggest that mastectomy and breast-conserving therapy produce similar outcomes among young women with early-stage breast cancer. Young women may wish to take this information into account when making decisions about breast cancer treatment.?

References: ??

[1] Buckley JM, Coopey S, Samphao S et al. Recurrence rates and long-term survival in women diagnosed with breast cancer at age 40 and younger. Paper presented at: 2011 Breast Cancer Symposium; September 8-10, 2011; San Francisco, CA. Abstract 70.?

[2] Mahmood U, Morris CG, Neuner GA et al. Equivalent survival with breast-conservation therapy or mastectomy in the management of young women with early-stage breast cancer. Paper presented at: 2011 Breast Cancer Symposium; September 8-10, 2011; San Francisco, CA. Abstract 85.?

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Breast-Conserving Therapy May Outperform Mastectomy Alone for Women with Early-Stage Triple-Negative Breast Cancers

For women with early-stage triple-negative breast cancer, treatment with breast-conserving surgery plus radiation therapy may result in fewer cancer recurrences in or near the breast than mastectomy without radiation therapy. These results were published in the Journal of Clinical Oncology.???

Breast cancers that are estrogen receptor-negative, progesterone receptor-negative, and HER2-negative are called triple-negative breast cancers. Triple-negative breast cancers tend to be more aggressive than other breast cancers and have fewer treatment options.???

For women with small breast cancers that have not spread to the lymph nodes, treatment often includes breast-conserving surgery (lumpectomy) plus radiation therapy or mastectomy (removal of the entire breast) without radiation therapy. These two approaches are generally thought to produce similar outcomes, but it’s possible that for certain subtypes of breast cancer one approach may be more effective than the other.?????

To compare breast-conserving therapy (lumpectomy plus radiation therapy) to mastectomy among women with early-stage (T1-2N0) triple-negative breast cancers, researchers evaluated information from 468 patients. The group was fairly evenly split in terms of how many had been treated with breast-conserving therapy and how many had been treated with mastectomy without radiation therapy.???

Study participants were followed for a median of 7 years. One of the outcomes of interest was locoregional recurrence. This refers to a recurrence of the cancer in the breast, chest wall, or nearby lymph nodes.???

Five-year survival without a locoregional recurrence was 96% among women treated with breast-conserving surgery and 90% among women treated with mastectomy without radiation therapy. In other words, women treated with breast-conserving therapy had a lower risk of recurrence in the breast, chest wall, or lymph nodes than women treated with mastectomy without radiation therapy.?At the time of the analysis, overall survival was similar in the two groups.?

Although additional studies are needed, it’s possible that adding radiation therapy may improve outcomes among women who undergo mastectomy for early-stage, triple-negative breast cancer. In the current study, the risk of recurrence within or near the breast was lower among women treated with breast-conserving therapy (lumpectomy plus radiation therapy) than among women treated with mastectomy without radiation therapy.????

Reference: Abdulkarim BS, Cuartero J, Hanson J et al. Increased risk of locoregional recurrence for women with T1-2N0 triple-negative breast cancer treated with modified radical mastectomy without adjuvant radiation therapy compared with breast-conserving therapy. Journal of Clinical Oncology. Early online publication June 13, 2011.?

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Hormone Replacement Therapy after Ovary Removal May be Safe for BRCA1/BRCA2 Carriers

For women with BRCA1 or BRCA2 gene mutations, use of hormone replacement therapy after preventive removal of the ovaries and fallopian tubes does not appear to increase the risk of breast cancer. These results were presented at the 2011 annual meeting of the American Society of Clinical Oncology.???

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.??

Options to manage this increased cancer risk include regular cancer screening, chemoprevention (use of medications to reduce risk), or preventive surgery (surgery to remove the breasts and/or ovaries before cancer is diagnosed).?

When performed by the time a woman is in her mid-30s or early 40s, preventive removal of the ovaries can substantially reduce the risk of both ovarian cancer and breast cancer. This reduction in cancer risk, however, comes at the cost of an early menopause and symptoms such as hot flashes, sleep disturbances, and vaginal dryness.??

Hormone replacement therapy (HRT) can effectively manage these symptoms, but it’s been uncertain whether this is safe for women with BRCA1/BRCA2 mutations. Studies in women without these mutations have indicated the combined (estrogen plus progestin) hormone therapy increases the risk of breast cancer.?

To evaluate the risk of breast cancer among BRCA1/BRCA2 carriers who have undergone preventive removal of their ovaries and fallopian tubes, researchers collected information from 795 women with a BRCA1 mutation and 504 women with a BRCA2 mutation. ?

????After ovary removal, breast cancer was diagnosed in 14% of the women who took HRT and 12% of the women who did not take HRT. This difference between groups was not statistically significant, suggesting that it could have occurred by chance alone. By comparison, risk of breast cancer was 22% among women who did not have their ovaries removed and did not take HRT.??

These results suggest that short-term use of HRT to manage menopausal symptoms may be an option for BRCA1/BRCA2 carriers who have had their ovaries removed. HRT did not significantly increase the risk of breast cancer in this population.????

Reference: Domchek SM, Friebl T, Neuhausen SL et al. Is hormone replacement therapy (HRT) following risk-reducing salpingo-oophorectomy (RRSO) in BRCA1 (B1) and BRCA2 (B2)-mutation carriers associated with an increased risk of breast cancer? Paper presented at: 2011 Annual Meeting of the American Society of Clinical Oncology; June 3-7, 2011; Chicago, IL. Abstract 1501.?

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