Category Archives: Breast Cancer

Intensity Modulated Radiation Therapy Reduces Risk of Side Effects in Breast Cancer Patients

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Newswise — Breast cancer patients treated with intensity modulated radiation therapy (IMRT) instead of standard whole breast irradiation (WBI) have a lower incidence of acute or chronic toxicities, according to a study in Practical Radiation Oncology (PRO), the official clinical practice journal of the American Society for Radiation Oncology (ASTRO).

Researchers are constantly conducting studies to determine the most effective breast cancer treatment that also reduces the incidence of potential side effects, including skin inflammation, swelling and infection.

Researchers in this study sought to compare standard WBI to WBI with IMRT (using both a typical treatment time and an accelerated treatment time) in terms of toxicity levels for patients. In a retrospective review, over 300 patients treated with one of the forms of radiation therapy were looked at and it was determined that radiation therapy using IMRT, regardless of the length of treatment, is associated with greatly reduced toxicities compared with the older, more standard radiation therapy technique.

A side analysis determined that larger breasted women had higher toxicity levels than smaller breasted women, however they still had reduced toxicities with IMRT over standard radiation, even though these levels were higher than smaller breasted women. This included IMRT with a shorter treatment time; previous trials usually exclude larger breasted women from receiving radiation using an accelerated treatment schedule.

“Our data support the increasing role of IMRT in delivering not only whole breast irradiation but also whole breast irradiation using an accelerated treatment time,” Frank Vicini, MD, a radiation oncologist with Michigan Healthcare Professionals/21st Century Oncology in Farmington Hills, Mich., said. “This is great news for breast cancer patients who, if eligible, can not only receive their radiation treatment in a shorter amount of time but also reduce their risk of many side effects.”

Report: New More-Sensitive Blood Test Catches Recurring Breast Cancer a Year Earlier

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Newswise — SAN DIEGO, March 28, 2012 Research was presented at a meeting of the American Chemical Society — A new blood test is twice as sensitive and can detect breast cancer recurrence a full year earlier than current blood tests, according to a scientist who reported here today at the 243rd National Meeting & Exposition of the American Chemical Society (ACS). The report was among more than 11,000 presentations on new developments in science scheduled this week at the meeting, held by the world’s largest scientific society.

Daniel Raftery, Ph.D., who reported on the test, pointed out that breast cancer survivors — 2.5 million in the U.S. alone — face about a 1-in-5 chance that the cancer will come back, or recur, within 10 years of treatment. Research shows that early detection of these recurrences and treatment can save lives. However, currently available blood tests are not very sensitive. Perhaps the best known test for a biological “marker” protein, or “biomarker,” called CA 27.29, misses many cases of recurrence and detects them late — often after symptoms, such as difficulty breathing or bone pain, surface.

“We have identified a group of nine biomarkers that signal recurrence of breast cancer,” Raftery said. “Our markers detect twice as many recurrences as the CA marker does at the same specificity. They also detect cancer recurrence earlier, about 11-12 months sooner than existing tests. They accomplish this with blood samples, rather than biopsies, with less discomfort to patients.”

To find these markers, Raftery’s team at Purdue University and Matrix-Bio, Inc., a company he founded, analyzed many hundreds of “metabolites” in the blood of breast cancer survivors. Metabolites are small molecules, biological byproducts formed as the body’s cells go about the business of life. Some are released into the bloodstream and urine. The rapidly emerging scientific field called “metabolite profiling” seeks to understand how these metabolites relate to health and disease. Groups of metabolites already have been linked to a range of diseases. Many of Raftery’s biomarkers were known to be involved in cancer. But no one knew that this group of metabolites could serve as biomarkers for breast cancer recurrence, he said.

The markers are detected with an instrument called a mass spectrometer, which is common in clinical laboratories. Raftery explained that these markers would be used in combination with results from CA 27.29 blood tests.

“We take both of those results together and roll them into the profile so that the score we generate is a combination of the CA value and our nine metabolites,” he said. “If the score indicates that the cancer probably has returned, the patient would then likely undergo imaging tests to locate the tumor.”

Raftery hopes that the new test will become available later this year. In the meantime, the researchers are conducting another clinical study with the test. He also said that, in the future, the test might be useful in the early detection of breast cancer, not just recurrences.

The scientists acknowledged partial funding from the National Institutes of Health.

Dietary Cadmium May Be Linked with Breast Cancer Risk

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Newswise — PHILADELPHIA — Dietary cadmium, a toxic metal widely dispersed in the environment and found in many farm fertilizers, may lead to an increased risk of breast cancer, according to a study published in Cancer Research, a journal of the American Association for Cancer Research.

Cadmium occurs at low concentrations naturally, but scientists are concerned because contamination of farmland mainly due to atmospheric deposition and use of fertilizers leads to higher uptake in plants.

“Because of a high accumulation in agricultural crops, the main sources of dietary cadmium are bread and other cereals, potatoes, root crops and vegetables,” said Agneta Åkesson, Ph.D., associate professor at Karolinska Institutet in Sweden. “In general, these foods are also considered healthy.”

For the current study, Åkesson and colleagues observed 55,987 women for more than 12 years. They estimated the dietary cadmium exposure using a food frequency questionnaire. During the follow-up period, researchers observed 2,112 incidences of breast cancer including 1,626 estrogen receptor-positive and 290 estrogen receptor-negative cases.

Cadmium consumption was divided into three groups with the highest levels of exposure compared with the lowest. Overall, a higher exposure to cadmium via diet was linked with a 21 percent increase in breast cancer. Among lean and normal weight women, the increased risk was 27 percent.

Both estrogen receptor-positive and negative tumors had the same risk increase at roughly 23 percent. Åkesson said that women who consumed higher amounts of whole grain and vegetables had a lower risk of breast cancer compared to women exposed to dietary cadmium through other foods.

“It’s possible that this healthy diet to some extent can counteract the negative effect of cadmium, but our findings need to be confirmed with further studies,” said Åkesson. “It is, however, important that the exposure to cadmium from all food is low.”

Study: Moderate red wine drinking may help cut women’s breast cancer risk

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LOS ANGELES – Drinking red wine in moderation may reduce one of the risk factors for breast cancer, providing a natural weapon to combat a major cause of death among U.S. women, new research from Cedars-Sinai Medical Center shows.

The study, published online in the Journal of Women’s Health, challenges the widely-held belief that all types of alcohol consumption heighten the risk of developing breast cancer. Doctors long have determined that alcohol increases the body’s estrogen levels, fostering the growth of cancer cells.

But the Cedars-Sinai study found that chemicals in the skins and seeds of red grapes slightly lowered estrogen levels while elevating testosterone among premenopausal women who drank eight ounces of red wine nightly for about a month.

White wine lacked the same effect.

Researchers called their findings encouraging, saying women who occasionally drink alcohol might want to reassess their choices.

“If you were to have a glass of wine with dinner, you may want to consider a glass of red,” said Chrisandra Shufelt, MD, assistant director of the Women’s Heart Center at the Cedars-Sinai Heart Institute and one of the study’s co-authors. “Switching may shift your risk.”

Shufelt noted that breast cancer is the leading type of women’s cancer in the U.S., accounting for more than 230,000 new cases last year, or 30 percent of all female cancer diagnoses. An estimated 39,000 women died from the disease in 2011, according to the American Cancer Society.

In the Cedars-Sinai study, 36 women were randomized to drink either Cabernet Sauvignon or Chardonnay daily for almost a month, then switched to the other type of wine. Blood was collected twice each month to measure hormone levels.

Researchers sought to determine whether red wine mimics the effects of aromatase inhibitors, which play a key role in managing estrogen levels. Aromatase inhibitors are currently used to treat breast cancer.

Investigators said the change in hormone patterns suggested that red wine may stem the growth of cancer cells, as has been shown in test tube studies.

Co-author Glenn D. Braunstein, MD, said the results do not mean that white wine increases the risk of breast cancer but that grapes used in those varieties may lack the same protective elements found in reds.

“There are chemicals in red grape skin and red grape seeds that are not found in white grapes that may decrease breast cancer risk,” said Braunstein, vice president for Clinical Innovation and the James R. Klinenberg, MD, Chair in Medicine.

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The study will be published in the April print edition of the Journal of Women’s Health, but Braunstein noted that large-scale studies still are needed to evaluate the safety and effectiveness of red wine to see if it specifically alters breast cancer risk. He cautioned that recent epidemiological data indicated that even moderate amounts of alcohol intake may generally increase the risk of breast cancer in women. Until larger studies are done, he said, he would not recommend that a non-drinker begin to drink red wine.

The research team also included C. Noel Bairey Merz, MD, director of the Women’s Heart Center, director of the Preventive and Rehabilitative Cardiac Center and the Women’s Guild Chair in Women’s Health, as well as researchers from the University of Southern California Keck School of Medicine and Hartford Hospital in Connecticut.

Source: Eurekalert

Risk for developing new cancer in other breast increased for survivors with BRCA mutation

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SAN ANTONIO — Breast cancer survivors who carry the BRCA1 or BRCA2 genetic mutation are at high risk for developing contralateral breast cancer — a new primary tumor in the other breast — and certain women within this group of carriers are at an even greater risk based on age at diagnosis and first tumor status, according to data presented at the 2011 CTRC-AACR San Antonio Breast Cancer Symposium, held Dec. 6-10, 2011.

“Our studies show that certain subgroups of women [with this mutation] who have already had cancers are also at risk for developing a second new cancer in their other breast, much more so than survivors who do not carry the mutation,” said Alexandra J. van den Broek, M.Sc., a doctoral candidate at the Netherlands Cancer Institute. “Our study is, as far as we know, the first study showing that within certain carriers of BRCA mutations, subgroups with an increased or decreased risk for contralateral breast cancer (CBC) can be made.”

Researchers surveyed 5,061 women diagnosed with unilateral, invasive breast cancer at 10 hospitals in the Netherlands. Two hundred eleven women (4.2 percent) were carriers of the BRCA1 or BRCA2 mutation. Overall, at a median of 8.4 years of follow-up, 8.6 percent of participants developed CBC.

Van den Broek and colleagues found that the overall 10-year risk for developing CBC in noncarriers was 6.0 percent, while risk for carriers was 17.9 percent.

For carriers diagnosed with their first breast cancer when aged younger than 40 years, the 10-year risk for CBC jumped to 26.0 percent. For carriers between the ages of 40 and 50 years at first diagnosis, the risk was 11.6 percent. In addition, mutation carriers with a triple-negative first tumor had a 10-year cumulative CBC risk of 18.9 percent compared with 11.2 percent among carriers with a non-triple-negative first tumor.

Although these numbers can be overwhelming to carriers who have already survived breast cancer, van den Broek said it is crucial to know who is most at risk and by how much.

“Guidelines for prophylactic measures and screening in the follow-up of patients with breast cancer carrying the BRCA1 or BRCA2 mutation are important to provide patients with the best information and counseling,” she said. “If these results are confirmed, [it will be] possible to personalize the guidelines for these specific subgroups.”

The next step will be to confirm the results in larger studies and to look at other factors that define subgroups of patients with an increased or decreased risk for CBC.

Source Eurekalert December 8 2011

Many women do not undergo breast reconstruction after mastectomy

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SAN ANTONIO — Despite the benefits, only a small minority of women, regardless of age, are opting for immediate reconstructive breast surgery after undergoing mastectomy for treatment of breast cancer, according to data presented at the 2011 CTRC-AACR San Antonio Breast Cancer Symposium, held Dec. 6-10, 2011.

Research has shown that immediate breast reconstruction after mastectomy improves psychological well-being and quality of life and provides women with improved body image and self-esteem compared with delaying the procedure.

However, data from this study, presented by Dawn Hershman, M.D., associate professor of medicine and epidemiology at Columbia University Medical Center in New York, indicate that only about one third of women undergo the procedure.

Hershman and colleagues identified 106,988 women with breast cancer who underwent mastectomy between 2000 and 2010. They identified these women using insurance codes and then examined data on the frequency of reconstruction by a number of factors including age, race, number of procedures performed in the hospital and type of insurance.

Of the women examined, 22.6 percent underwent immediate reconstruction. Although overall rates of reconstruction have increased since 2000, the greatest increases were seen among women with commercial insurance — from 25.3 percent to 54.6 percent — and among women aged younger than 50 years — from 29 percent to 60 percent. Among women aged 50 years or younger who also had commercial insurance, 67.5 percent underwent immediate breast reconstruction. Overall, women with commercial insurance had more than a threefold higher likelihood of undergoing immediate reconstruction compared with women without health insurance.

“We were surprised to see that although the use of immediate postmastectomy reconstruction has increased, the rates still remain low, with 41.8 percent of women aged younger than 50 years and less than 20 percent of women aged older than 50 years receiving reconstruction during this time frame,” Hershman said.

Researchers found that patients were more likely to undergo immediate reconstruction if their surgeon did more mastectomies or they were in a hospital where more mastectomies were performed.

“This is something that could be modified by training and patient education,” Hershman said.

Other factors associated with a decreased likelihood for undergoing mastectomy were increasing age, black race, rural hospital location, nonteaching hospital or having other medical illnesses.

Women who underwent immediate breast reconstruction postmastectomy did have a longer hospital stay, but in-hospital complication rates were similar between women who had reconstruction and those who did not.

“Our study shows that there are factors that can be modified to increase the likelihood that women undergo postmastectomy reconstruction,” Hershman said. “Public policy should ensure that access to reconstructive surgery is available to all women regardless of insurance status.”

In the future, Hershman and colleagues plan to explore other factors that may be associated with immediate reconstruction to better target interventions to appropriate institutions.

Source Eurekalert December 8 2011

Obese patients with HER2-positive breast cancer may have worse outcomes

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SAN ANTONIO — Obese patients with early-stage HER2-positive breast cancer may have worse outcomes than patients who are normal weight or overweight, Mayo Clinic researchers found in a study presented today at the 2011 CTRC-AACR San Antonio Breast Cancer Symposium. HER2-positive breast cancer gets its name from a protein called human epidermal growth factor receptor 2 that promotes cancer cell growth.

“Not only did obese women have poorer outcomes given several different therapies tested to treat HER2-positive breast cancer, but we know that obese patients in our study had larger tumors and were more likely to have had cancer detected in their lymph nodes, compared to patients who were not obese,” says the study’s lead author, Jennifer Crozier, M.D., a medical resident.

“While other studies have looked at the effect of body weight on treatment outcome for estrogen receptor-positive breast cancer, no one has examined this variable in the HER2-positive subtype, which accounts for about one-third of all breast cancers,” says Dr. Crozier.

Researchers used data from the North Central Cancer Treatment Group N9831 study for their analysis. This phase III randomized clinical trial tested three different options for treatment of early stage HER2-positive breast cancer: chemotherapy alone (Arm A); chemotherapy followed by Herceptin for a year (Arm B); and chemotherapy plus Herceptin, followed by Herceptin for a year (Arm C).

In a review of data from 3,017 patients, researchers found that, considering all three treatment arms together, obese patients — those with a body mass index (BMI) of 30 or more — had worse outcomes than patients with a BMI less than 30, although these trends were not statistically significant.

Researchers then calculated disease-free survival for each study arm for normal weight, overweight and obese patients, and found that patients fared best in Arm C. In this arm, the difference between BMI and outcome was not statistically significant, Dr. Crozier says. Herceptin was powerful enough to provide an equal benefit in patients with vastly varying body weights, she says.

“We are continually searching for approaches that will help our patients have the best outcome possible after their diagnosis of breast cancer, and this study suggests that excess body weight may make a difference,” says senior investigator Edith Perez, M.D., director of Mayo Clinic’s breast program in Florida.

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The study was funded by the National Institutes of Health, Genentech, Bayer, and the Breast Cancer Research Foundation.

Source: Eurekalert December 8 2011

Researchers find genetic rearrangements driving 5 to 7 percent of breast cancers

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ANN ARBOR, Mich. — Researchers at the University of Michigan Comprehensive Cancer Center have discovered two cancer-spurring gene rearrangements that may trigger 5 to 7 percent of all breast cancers.

These types of genetic recombinations have previously been linked to blood cancers and rare soft-tissue tumors, but are beginning to be discovered in common solid tumors, including a large subset of prostate cancers and some lung cancers.

Looking at the genetic sequencing of 89 breast cancer cell lines and tumors, researchers found two distinct types of genetic rearrangements that appear to be driving this subset of breast cancers. The recurrent patterns were seen in the MAST kinase and Notch family genes. The findings were published online in Nature Medicine ahead of print publication.

“What’s exciting is that these gene fusions and rearrangements can give us targets for potential therapies,” says Arul Chinnaiyan, M.D., Ph.D., director of the Michigan Center for Translational Pathology, Howard Hughes Medical Institute Investigator, and S.P. Hicks Professor of Pathology at the U-M Medical School. “This is a great example of why treating cancer is so challenging. There are so many different ways genes get recombined and so many molecular subtypes, that there’s not one solution that will work for all of them.”

“The research provides additional evidence that these types of genetic rearrangements seem to be a significant cause of solid tumors,” he adds.

The discoveries illuminate a promising path for future research, Chinnaiyan says. Gene sequencing offers opportunities to develop treatments for individuals whose tumors carry specific genetic combinations – a process commonly known as “personalized medicine.”

The study demonstrated that the genetic rearrangements had profound effects on breast cancer cells in the lab, both in tissue culture and in mouse models.

“We cloned each of these rearrangements and introduced them into normal breast cell lines, where they appeared to have cancer-causing effects,” Chinnaiyan says.

Previous U-M research showed that half of prostate cancers have a genomic rearrangement that causes the fusion of two genes called TMPRSS2 and ERG. This gene fusion, believed to be the triggering event for these prostate cancers, was initially discovered in 2005 by U-M researchers led by Chinnaiyan.

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Additional authors: Dan R. Robinson, Shanker Kalyana-Sundaram, Yi-Mi Wu, Sunita Shankar, Xuhong Cao, Bushra Ateeq, Irfan A. Asangani, Matthew Iyer, Christopher A. Maher, Catherine S. Grasso, Robert J. Lonigro, Michael Quist, Javed Siddiqui, Rohit Mehra, Xiaojun Jing, Thomas J. Giordano, Michael S. Sabel, Celina G. Kleer, Nallasivam Palanisamy, Chandan Kumar-Sinha, all of U-M. Kalyana-Sundaram also of Bharathidasan University, Tiruchirappalli, India

Rachael Natrajan, Maryou B. Lambros, Jorge S. Reis-Filho, of the Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, London, UK.

Disclosures: The researchers report no conflicts of interest. U-M has filed for patent protection for these developments.

Funding: The specific aims of this project were supported by the Department of Defense Breast Cancer Research Program. The project was also supported in part by an American Association for Cancer Research Stand Up to Cancer (SU2C) breast cancer award, the National Functional Genomics Center supported by the Department of Defense, and the National Institutes of Health. Chinnaiyan is supported by the National Cancer Institute Early Detection Research Network, the Doris Duke Charitable Foundation and the Burroughs Welcome Foundation; he is also an American Cancer Society research professor and Taubman Scholar.

Source: Eurekalert

Increase in postmastectomy breast reconstruction

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Released: 10/18/2011 11:00 AM EDT

Source: American College of Surgeons (ACS)

New findings show an increase in postmastectomy breast reconstruction, and that TRAM flap reconstruction remains intact with a high degree of patient satisfaction

Newswise — SAN FRANCISCO: Until now, studies looking at trends in cancer care have shown that immediate postmastectomy breast reconstruction has been underutilized. But a pair of studies presented today at the 2011 Annual Clinical Congress of the American College of Surgeons indicate that the number of women undergoing breast reconstruction procedures has almost doubled between 1998 and 2007. Furthermore, the first study points to successful results from a surgical technique called TRAM (Transverse Rectus Abdominis Myocutaneous) flap with a minimum of 15 to 29 years of follow-up after the procedure, while the second study identifies which women were most likely to undergo reconstruction procedures.

Breast reconstruction is a surgical procedure that restores shape to the breast after mastectomy. There are two types of breast reconstruction—autologous and implant-based. A TRAM flap operation is an autologous reconstruction that involves taking abdominal tissue and relocating it to the chest to build a natural-looking breast.

As reported on at the Clinical Congress, Chris D. Tzarnas, MD, FACS, senior author and professor of surgery, Temple University School of Medicine, Philadelphia, and his colleagues reviewed the outcomes of 217 women who underwent TRAM flap breast reconstruction between 1982 and 1996. Most of the women, average age 51, underwent the reconstruction procedure immediately following a mastectomy. The point of the study, Dr. Tzarnas explained “was to assess the long-term outcomes. This is the longest follow-up for this type of reconstruction in the literature to date.” After examining medical records and conducting interviews with the patients 15 to 29 years after the procedures, researchers found that the reconstructions were still intact, and very few women required additional operations, unlike implant-based reconstructions, which often rupture or harden over time. More important, from a quality of life perspective, all of the women felt good about themselves after the TRAM procedure.

“The best reconstructions are those that try to replace everything that is removed. And that has been and, I think, continues to be using the TRAM flap,” Dr. Tzarnas said. “It’s good to show that these reconstructions are doing well and holding up long term.”

On another front, researchers from NorthShore University HealthSystem, Evanston, IL, wanted to look at the reasons breast reconstruction procedures have been underutilized in the past. In their analysis, lead researcher Mark Sisco, MD, a clinical assistant professor of surgery at the University of Chicago Pritzker School of Medicine and his team examined data from the National Cancer Data Base (NCDB) of the American College of Surgeons and the American Cancer Society, a nationwide oncology outcomes database for more than 1,500 Commission on Cancer- accredited cancer programs in the United States and Puerto Rico.

Dr. Sisco and his team sought to conduct a follow-up study of one led by Monica Morrow, MD, FACS, and published in the Journal of the American College of Surgeons in January 2001.*

Dr. Sisco and colleagues found that although the use of breast reconstruction, both autologous and implant-based, actually increased from 12 to 23 percent between 1998 and 2007, some populations of women still are not undergoing reconstructive procedures at the same rate as others.

To identify factors influencing the use of immediate and early breast reconstruction (within 90 days post-mastectomy), they evaluated data on 396,434 women who underwent mastectomy for invasive breast cancer between 1998 and 2007. Then, they compared two cohorts of patients: 134,479 women who had a mastectomy between 1998 and 2000 to 105,114 women who had a mastectomy between 2005 and 2007.

After accounting for tumor characteristics, they found that overall, women who were not African American; had private insurance; were cared for in an academic medical center; resided in large metropolitan communities; and lived in higher-income areas were up to twice as likely to undergo breast reconstruction during both time periods. Despite the overall increase in utilization, none of these disparities have significantly narrowed over both time periods.

“We are doing better at getting reconstruction to women, which is terrific, but it’s clear that we haven’t done a very good job of narrowing the gap in patients who have lower socioeconomic status or live in smaller communities,” Dr. Sisco observed.

Medical guidelines for breast reconstruction are a work in progress, he explained. The guidelines have changed over the years and future change is certain. “Our study really underscores the importance of continuing efforts to improve access to reconstructive surgery, in part by educating both the providers that it’s safe for women to have immediate post mastectomy breast reconstruction and the patients that breast reconstruction is not considered cosmetic surgery,” said Dr. Sisco.
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NOTE: Both of these studies on postmastectomy breast reconstruction were designated as “Posters of Exceptional Merit” at the ACS Clinical Congress.

Dr. Tzarnas’ co-authors included Wendie Grunberg, DO; R. Barrett Noone, MD, FACS; Andres Mascaro, MD; Azra Ashraf, MD; and Emilia Diego, MD. Dr. Tzarnas’ study was not funded and the data analyzed was obtained from medical records.

Dr. Sisco’s co-authors included Hongyan Du, MS; Karol A. Gutowski, MD; David H. Song, MD, FACS; David J. Winchester, MD, FACS; Kathy Yao, MD, FACS; Jeremy P. Warner, MD; and Michael A. Howard, MD. The study was supported by data provided by the division of plastic surgery, NorthShore University HealthSystem and by the American College of Surgeons National Cancer Database access site.

*Morrow, M et al. “Factors influencing the use of breast reconstruction postmastectomy: a national cancer databgase study.” J Am Coll Surg. 2011 Jan:1-8.

Through-the-Nipple Breast Cancer Therapy Shows Promise in Early Tests

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October 26 2011

Newswise — Delivering anticancer drugs into breast ducts via the nipple is highly effective in animal models of early breast cancer, and has no major side effects in human patients, according to a report by Johns Hopkins Kimmel Cancer Center researchers in Science Translational Medicine on October 26. The results of the study are expected to lead to more advanced clinical trials of so-called intraductal treatment for early breast cancer.

“Our results support the theory that by treating the breast tissue directly we can reach a much more potent drug concentration where it is needed, with far fewer adverse effects on tissues outside the breasts,” says oncologist Vered Stearns, M.D., Ph.D., the Breast Cancer Chair in Oncology and co-director of the Breast Cancer Program at the Kimmel Cancer Center, who supervised the clinical part of the study.

“This has been a classic translational medicine collaboration between a bench researcher and a clinician scientist,” says cancer biologist Saraswati Sukumar, Ph.D., who supervised the animal tests.

Sukumar, the Barbara B. Rubenstein Professor of Oncology at the Kimmel Cancer Center, and co-director with Stearns of the Breast Cancer Program, began intraductal research more than a decade ago, reasoning that because most breast cancers originate from cells lining the milk ducts, early or preventive therapies should be delivered directly to the ducts via the nipple, rather than intravenously. In 2006, in the journal Cancer Research, Sukumar and her colleagues reported on an initial successful test of the technique using the chemotherapy drug doxorubicin against early ductal breast cancers in rats.

For the current study, Stearns set up a small clinical trial to determine the feasibility of Sukumar’s technique in 17 breast cancer patients. Starting first with dextrose — essentially sugar water — and later with escalating doses of the same doxorubicin formulation used on Sukumar’s rats (pegylated liposomal doxorubicin, or PLD), she was able to infuse patients’ breast ducts via a small catheter placed into the nipple. The technique wasn’t used in this case to treat cancer; the patients in the study all had established breast tumors and were awaiting mastectomies. But Stearns was able to establish that single doses of PLD to breast ducts caused only mild side effects including mild nipple pain and breast fullness.

A comparison of 12 patients receiving PLD intraductally with three patients treated with PLD by the standard intravenous route also was revealing, Stearns said. “Intraductal delivery of PLD resulted in much higher concentration in the breast compared to the circulation, whereas in the women with intravenous doses we saw relatively high concentrations in the blood but very little if any in the breast,” she noted.

In the animal portion of the study, Sukumar’s lab examined the intraductal effectiveness of four standard anticancer drugs, 5-fluorouracil (5FU), carboplatin, methotrexate and paclitaxel, all compared with PLD. Of these drugs, intraductal 5FU prevented the most cancers compared to no drug or to intravenous delivery. It also shrank established breast tumors with striking effectiveness, completely eliminating them in 10 of 14 treated rats, she said. “As both a preventive and a therapy, 5FU worked extremely well in these tests,” Sukumar added.

5FU has the additional advantage, she noted, of sparing breast ducts the kind of damage caused by PLD, which at therapeutic doses can destroy large parts of the ductal lining. But perhaps the most intriguing outcome of these tests, she said was that preventive treatment of only four mammary glands in rats — who have a total of twelve — showed a strong effect in preventing tumors in the untreated glands as well. “We think that 5FU, at the high concentration achieved with intraductal delivery, elicits an immune response that can suppress tumor formation in the other ducts,” Sukumar said. “This is an attractive feature, because some breast ducts in women are ‘blind ducts’ that are unconnected to the nipple and therefore unreachable directly with intraductal therapy.”

Sukumar and Stearns say the next step is to set up a further clinical study with 5FU, based on the new findings. The goal is to use intraductal therapy to suppress tumors in patients with a high genetic risk for breast cancer or premalignant lesions in their breast ducts. “In principle, one could do such a procedure every ten years or so to keep one’s breasts tumor-free, as an alternative to having the breasts removed,” Sukumar says.

The study was funded by the National Cancer Institute, Windy Hill Medical Center, the Mary Kay Ash Foundation and the Susan Love Research Foundation.

Other contributors to the study, besides Drs. Sukumar and Stearns, were co-first author Tsuyoshi Mori, currently at the Shiga Institute of Medical Science in Japan; and Lisa K. Jacobs, Nagi F. Khouri, Edward Gabrielson, Takahiro Yoshida, Scott L. Kominsky, David L. Huso, Stacie Jeter, Penny Powers, Karineh Tarpinian, Regina J. Brown, Julie R. Lange, Michelle A. Rudek, Zhe Zhang and Theodore N. Tsangaris, all of Johns Hopkins.