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A publication for the NYU Langone Medical Center Community September/October 2010
"The Future Looks Bright"
By Freya Schnabel, MD
(Director of Breast Surgery NYU Langone Medical Center)
(This speech was presented by Dr. Schnabel at The Second Japanese Breast Cancer Symposium @ Yokohama, Japan 7/10/2010)
Perspectives: History of science, history of patients’ rights, increasingly complex treatments, clinical trials, patient advocacy
First, I would like to thank Makiko Yamamoto of the Young Japanese Breast Cancer Network organization and all the organizers of this conference for the opportunity to be with you today. And I’d like to thank all the participants in this conference for coming here today and showing their commitment to the cause of improving the lives of women with breast cancer in Japan and throughout the world. Usually, when I give a lecture about breast cancer, I rely on scientific evidence to make my arguments. I show many slides with tables and graphs, and I discuss the data represented using statistical terms. But today, I am here to talk about a topic that is extremely important to the lives of women with breast cancer, yet cannot be discussed in scientific and statistical terms. I have been asked to discuss physician-patient communication and breast cancer advocacy.
In the time before modern diagnostic and treatment methods, it was not terribly important for individuals to understand the nature of their illnesses. In fact, many times, the practitioner who treated them had little understanding of the science of normal human biology and pathophysiology. With increasing knowledge about the underlying causes of diseases, there was increasing opportunity for physicians to educate their patients, particularly when preventable causes for diseases could be identified. The earliest examples of this have to do with infectious diseases and epidemics. When the causes for cholera and yellow fever were identified, informing the public was critically important in order to prevent spread of these diseases. It is possible that these public health measures, undertaken to prevent the spread of epidemics, are the first example of the medical profession recognizing the critical importance of informing the public and eliciting the participation of non-professionals in changing outcomes.
Since that time, we have uncovered many other examples of diseases that can clearly be prevented or modified based on the participation of the patient. Some common examples are diabetes and heart disease, where diet and exercise (requiring patient commitment and participation) are so important to improve the outcomes of the diseases. In order for patients to comply with the recommendations for diet and exercise, etc. it is obvious that they need to be informed and educated by their physicians and other medical providers regarding the benefits of lifestyle modifications. This requires dialogue between physicians and patients, a giving and taking of information.
So, one general benefit of physician-patient communication is helping patients understand how to change their lifestyles to prevent or modify their chances of developing a disease.
2. Patients’ Rights perspective
Our societies have placed increasing emphasis on the rights of individuals. Modern societies have taken great pains to describe the rights of individuals to be autonomous and self-determining. This has led to significant emphasis in the US on patients’ rights. Every hospital has to prominently display a “Patient’s Bill of Rights” enumerating a variety of rights every patient should expect to receive while being treated. These rights include the right to know who is treating them and the details of the proposed treatment.
We are required to obtain “informed consent” for all invasive procedures. Informed consent is a conversation where the patient is informed as to the reasons for the proposed procedure, along with the risks, benefits and alternatives of treatment.
In order for a patient to give genuine informed consent, the patient must understand the illness for which she is being treated, along with the details of the treatment and the possible outcomes. Without this understanding, there is no informed consent. This is certainly a legal issue, and in the US, health care providers can be sued for malpractice for performing procedures without the patient’s consent. It is also an ethical and moral issue.
Sometimes, the lines that appear so clear cut may be a bit blurry. Occasionally, a family will request that an elderly individual not be informed as to the details of a diagnosis, especially a malignant or life-threatening one, in order to spare their feelings and avoid any possible emotional consequences of receiving bad news. This “Don’t Tell Mama” syndrome is more common in certain ethnic and religious communities.
When I was new in medical practice, I felt strongly that withholding information from any patient was entirely wrong. At this point, I can admit that there are situations where it may be reasonable to modify how much information is shared with certain patients, and I am willing to let the patient (not the family) dictate how much information they are capable of hearing without being overwhelmed.
However, I always remind families that even if they think the patient does not know that they are sick, or doing poorly, people usually know. And it may be extremely stressful for everyone concerned to keep these toxic secrets. At this point, a patient who is not fully informed about her illness cannot give informed consent to any treatment or procedure. Being poorly informed takes away an individual’s rights to make decisions on their own behalf. And being kept in the dark about an illness may add unnecessary stress to a patient’s experience of her illness. Without complete information, a patient may feel a loss of control, a loss of empowerment, because she feels she is somewhat in the dark and lacks important facts that others (including her doctors) possess. So, appropriate physician-patient communication helps preserve an individual’s rights for self determination, allows the patient to fully consent to treatments and takes away the stress that comes with feeling a loss of power and control.
The treatments we offer patients with breast cancer have become increasingly complex, and involve multiple different modalities, including surgery, radiation therapy and an expanding variety of medical treatments, including chemotherapy, hormonal therapy and targeted therapies such as Herceptin. With this level of complexity, it is imperative to have an open discussion between physician and patient that reviews the details of the various treatments and their risks and benefits. Multiple studies have demonstrated that patients who understand their treatments are able to better comply with the treatment regimens. In my observation, patients who are well informed about their treatments are also better able to manage the side effects. Understanding why a treatment is being prescribed, and the benefit that it is expected to bring, helps a patient understand the importance of adhering to the regimen.
The best example of information and education ensuring compliance is the clinical trial. We all know that clinical trials are vitally important and have advanced our breast cancer treatments immeasurably in the last several decades. In order for a patient to enroll in a clinical trial, she must be informed about the trial in great detail, including the benefits and risks of the treatment. Only then can she give consent and be included in the trial.
If this concept of patient education and information is critical to consent to a clinical trial, it must be equally important for patients who are consenting to conventional treatment. Once again, we can see how open communication between physicians and patients leads to better outcomes, both in exploring new treatments and in adhering to all treatments, both new and established.
Last, but not least, the concept of patient advocacy has made an enormous contribution to the evolution of the doctor-patient relationship in the US, and I hope, in Japan. Patient advocacy groups in America helped disseminate information about breast conserving surgery – perhaps even before some in the medical community were ready to believe the data and embrace this new approach. Advocacy groups such as Susan G. Komen for the Cure have helped secure increased US governmental funding for breast cancer research over the past 20 years. These groups have raised consciousness about the importance of breast cancer screening in America, and have made concerted efforts to expand access to mammography for all women. The contributions of these advocacy groups are beyond measure.
The advocacy groups have emphasized the importance of patient input into medical decision making, and have been responsible in the US for the requirement of patient advocates in the review process for clinical trials. The perspective of the patient is thereby incorporated into trial design and monitoring of outcomes. Advocacy groups have insisted that patient voices be heard and helped us remember that we must never treat the disease while neglecting the interests of the person who has the disease. Advocacy groups represent the epitome of physician-patient partnership – the idea that when both physicians are fully engaged in the process, we can have our outcomes.
Clearly, physicians and scientists and women all over the world, when they work together, have the best opportunity to defeat breast cancer and remove the threat of this disease from the lives of women of future generations.
I am delighted to be here today and emphasize that as a practicing breast surgeon, I encourage my patients to participate fully in their care. I feel obligated to inform them fully regarding the options of treatment open to them, and I expect them to ask questions and discuss the topic with me until they are able to make decisions that are right for them. I see better compliance in patients who are informed and engaged in their treatment.
And I recognize the role that advocacy groups have played in furthering the search for a cure for breast cancer. I encourage all of you here today to continue to involve yourselves in the struggle against breast cancer, and I applaud the work of the Young Breast Cancer Network.
Thank you for your attention today, and I look forward to the panel discussion.
Lobular carcinoma in situ, the other preinvasive disease
Despite its name, lobular carcinoma in situ (LCIS) technically isn't breast cancer, and it may not even be a precancerous condition. However, it is generally considered a risk factor for the disease. Although a handful of small studies (most including fewer than 200 women) have suggested that LCIS doesn't directly progress to invasive cancer, women with LCIS are four times more likely than average to develop invasive ductal cancer and 18 times more likely to develop invasive lobular cancer.
LCIS is a proliferation of abnormal cells in the milk-producing structures (lobules) of the breast. The incidence of LCIS has been rising steadily since the late 1980s, mostly among women ages 50 and over. And since 2000, incidence has increased only among those ages 50 to 69 — the group most likely to have regular mammograms.
LCIS doesn't produce lumps that can be felt during breast exams or microcalcifications that appear on a radiology screen. It's usually discovered by chance during a biopsy for a benign breast condition or an invasive form of cancer. It occurs in an estimated 0.5% to 3.8% of benign breast biopsies, but no one knows for certain how common it really is.
LCIS usually arises in several lobules of both breasts, so lumpectomy isn't an option. Instead, LCIS is managed in these ways:
Future directions in DCIS
DCIS research is directed mainly at improving treatment and, above all, at preventing progression to invasive disease. As researchers continue to study the pathology of DCIS, they are finding that certain tumor characteristics help predict the treatment most likely to reduce the chance of recurrence. For example, some forms of breast cancer require estrogen in order to grow; tumors that do are termed estrogen receptor–positive (ER-positive). Tamoxifen belongs to a class of drugs called selective estrogen-receptor modulators (SERMs), which act by blocking estrogen receptors. Tamoxifen is more likely to prevent a recurrence in women with ER-positive DCIS than in women with ER-negative disease.
The use of aromatase inhibitors, which block estrogen production in the peripheral tissues and breast tissue, is being investigated in a trial of postmenopausal women with ER-positive DCIS. For women whose DCIS is ER-negative but who have the HER-2/neu gene, researchers are exploring the use of trastuzumab (Herceptin) and lapatinib (Tykerb), which block the tumor growth factors produced by that gene.
Another promising area of investigation involves the short-term use of chemotherapy between diagnosis and surgery to alter the DCIS, so that tissue from the surgical resection can be used by researchers to assess molecular as well as pathologic evidence of response. Agents that can induce responses in the "right direction" — for example, slow or stop the growth of abnormal cells — may then be further evaluated for their potential in treatment or prevention.
A new way to administer radiation that is showing some promise in clinical trials is accelerated partial breast irradiation, in which the tumor site alone is treated for five days with a lighter dose of radiation. In another approach, intraoperative radiation therapy, a one-time dose of radiation is delivered to the involved area of the breast after the tumor has been removed but before the incision is closed.
The good news about DCIS
DCIS is sometimes classified as Stage 0 of breast cancer, the earliest stage of the disease. The question for women with this diagnosis is not "Will I live?" but "How much treatment will I need?" One of the biggest risks today is overtreatment. That, too, is changing, as researchers get better at distinguishing the types of tumors that can be subdued without extensive surgery or radiation. DCIS is one cancer that can truly be considered curable.
If you have DCIS, you might consider entering a clinical trial. You would get the best available care and might benefit from a new type of therapy or approach. At the very least, you would be contributing to much-needed knowledge about this condition. Check the National Cancer Institute's registry of clinical trials at www.cancer.gov/clinicaltrialswww.cancer.gov/clinicaltrials for a site near you.
Harvard Women's Health Watch | September 2008
In the journals
Hot flashes and sleep disturbances are a common and often severe side effect of drugs used to treat and prevent breast cancer, including tamoxifen and aromatase inhibitors. Estrogen is the best way to relieve hot flashes, but it can fuel breast cancer growth, so women who’ve had breast cancer or are at increased risk for it should usually avoid hormone therapy. Other options — less effective and with side effects of their own — include herbal therapies and prescription medications such as antidepressants and the anti-epileptic drug gabapentin. Now, in a small pilot study of breast cancer survivors, researchers have found they can nearly eliminate severe hot flashes and nighttime awakenings, with virtually no side effects, by anesthetizing certain nerves in the neck — a procedure called stellate ganglion blockade (SGB). The findings, published in Lancet Oncology (June 2008), may also have implications for menopausal women with disabling hot flashes.
While its application to hot flashes is relatively new, SGB has been safely used for years to relieve pain in the face, head, neck, and upper arm. During the procedure, an anesthetic is injected into the stellate ganglion (see illustration), a cluster of nerve cells in the neck that help regulate blood flow and are linked to brain regions involved in body temperature regulation.
In the investigation, led by Dr. Eugene Lipov at Advanced Pain Centers in Hoffman Estates, Ill., 13 women whose breast cancer was in remission underwent x-ray image–guided SGB in the right side of the neck. The 10-minute procedure was performed under local anesthesia with optional mild sedation. For a week before and 12 weeks after treatment, the women logged the frequency and severity of their symptoms. Two weeks after the procedure, hot flashes had decreased from an average of 80 per week to 50, and night awakenings from 20 per week to seven. By the end of the three-month follow-up period, night awakenings were down to about one per week, and the women were having almost no hot flashes at all. Five of the women required only one SGB procedure, and the other eight required two. There were no adverse effects except Horner’s syndrome, a drooping eyelid that lasts for a few hours after the procedure and indicates that the blockade was properly placed.
The investigators concede that their findings are preliminary and more research is needed to prove that SGB will be effective and without complications for breast cancer survivors. (Lipov’s group published similar results in a handful of women with postmenopausal hot flashes in the October 2005 Journal of Women’s Health.) There are some drawbacks to the procedure: it requires special training to perform; it’s expensive (between $1,000 and $3,000); it’s not always covered by health insurance; and injected anesthetics could cause allergic or other adverse reactions. In future studies, the researchers will evaluate the safety and effectiveness of applying pulsed radiofrequency instead of injected anesthetics to the stellate ganglion.
2. New Choices in Breast Reconstruction
3. Goals of Reconstruction
4. Special Considerations in Breast Reconstruction
5. Types of Breast Reconstruction
6. Nipple and Areola Reconstruction
7. Your Plastic Surgeon
8. Before Surgery
9. After Breast Reconstruction Surgery
10. Breast Reconstruction and Cancer Recurrence
11. Our Reach to Recovery Program
13. Additional Resources
Breast reconstruction is a surgical procedure to restore the appearance of a breast for women who have had a breast removed (mastectomy) to treat breast cancer. The surgery rebuilds the breast so that it is about the same size and shape as it was before it was removed. The nipple and areola (the darker area surrounding the nipple) can also be added. Most women who have had a mastectomy can have reconstruction. Women who have had a lumpectomy usually do not need reconstruction. Breast reconstruction is done by a plastic surgeon.
This information is designed to give you the facts you need to make an informed decision about breast reconstruction. It will help you better understand the process and the words used when talking about breast reconstruction. The words in italics are further explained in the glossary at the end of this information.
The decision to have breast reconstruction is a matter of personal choice. Learn as much as you can about the process before making a decision. No single source of information can provide every fact or give you all the answers. You and those close to you should discuss any questions and concerns about reconstructive surgery with your health care team.
2. New Choices in Breast Reconstruction
Each year more than 240,000 American women face the reality of breast cancer. Today, the emotional and physical results are very different from what they were in the past. Great strides have been made in our understanding of this disease and its treatment. New approaches in treatment, as well as advances in reconstructive surgery mean that women who have breast cancer today have new and better choices.
More and more women with breast cancer are choosing surgery that removes less breast tissue than a mastectomy (removal of the entire breast). This is called breast conservation surgery (or lumpectomy or segmental mastectomy). However, some women choose (or need) a mastectomy. Some of those who have a mastectomy also choose to have reconstructive surgery to restore the breast's appearance.
If you are thinking about having reconstructive surgery, it is a good idea to discuss it with your surgeon and a plastic surgeon experienced in breast reconstruction before your mastectomy. This allows the surgical teams to plan the treatment that is best for you, even if you decide to wait and have reconstructive surgery later.
3. Goals of Reconstruction
Women choose breast reconstruction for different reasons. The goals of reconstruction are:
* to make your breasts look balanced when you are wearing a bra
* to permanently regain your breast contour
* to give the convenience of not needing an external prosthesis
The difference between the reconstructed breast and the remaining breast can be seen when you are nude. When the breasts are in a bra though, they should be close enough to one another in size and shape that you will feel comfortable about how you look in most types of clothing.
Your body image and self-esteem may improve after your reconstruction surgery, but this is not always the case. Breast reconstruction does not fix things you were unhappy about before your surgery. Also, you may be disappointed with how your breast looks after surgery. You and those close to you must be realistic about what to expect from reconstruction.
You should decide to have breast reconstruction only after you are fully informed about the procedure. There are often many options to think about as you and your doctors discuss what is best for you. The reconstruction process may require one or more operations. You should talk about the benefits and risks of reconstruction with your doctors before the surgery is planned. Give yourself plenty of time to make the best decision for you.
4. Special Considerations in Breast Reconstruction
Several types of operations can be done to reconstruct your breast. You can have a newly shaped breast with the use of a breast implant, your own tissue flap, or a combination of the two. A tissue flap is a section of your own skin, fat, and muscle which is moved from your tummy, back, or other area of your body to the chest area.
Immediate or Delayed Reconstruction with Breast Cancer
Immediate reconstruction is done at the same time as the mastectomy. A plus with immediate reconstruction is that the chest tissues are undamaged by radiation therapy or scarring. Also, immediate reconstruction means one less surgery.
Delayed reconstruction is done at a later time. For some women, this may be advised if radiation to the chest area is needed after the mastectomy. This is because radiation therapy that follows breast reconstruction can increase complications after surgery.
Decisions about reconstructive surgery depend on many personal factors such as:
* your overall health
* the stage of your breast cancer
* the size of your natural breast
* the amount of tissue available (for example, very thin women may not have
enough extra body tissue to make flap grafts possible)
* your desire to match the appearance of the opposite breast
* your desire for bilateral reconstructive surgery and your insurance coverage for
the unaffected breast and related costs
* the type of procedure
* the size of implant or reconstructed breast
Other important factors to consider:
* You may not want to think about this issue while you are coping with a diagnosis of cancer. If this is the case, you may choose to wait until after your breast
cancer surgery to decide about reconstruction.
* You may simply not want to have any more surgery than is needed.
* Scarring is a natural outcome of any surgery, but skin necrosis (cell death) may
occur if your ability to heal is impaired.
* Not all surgery is completely successful, and you may not be pleased with your
* You may be concerned if you have bleeding or scarring tendencies.
* Your ability to heal may be hindered by previous surgery, chemotherapy,
radiation, smoking, alcohol, diabetes, various medicines, and other factors.
* Is it your preference to have chemotherapy or radiation therapy after
reconstruction or wait and have surgery after all treatment is completed?
* Breast reconstruction restores the shape of the breasts but cannot restore
your normal breast sensation. With time, the skin on the reconstructed breast
can become more sensitive, but it will not give you the same kind of pleasure as
before a mastectomy.
* Surgeons may suggest you wait for one reason or another. This may happen if
you smoke or have other health conditions. Many surgeons require you to quit
smoking at least 2 months before reconstructive surgery to allow for better
healing. You may not be able to have reconstruction at all if you are obese, too
thin, or have circulatory problems.
* The surgeon may recommend surgery to reshape the remaining breast to match
the reconstructed breast. This could include reducing or enlarging the size of the
breast or lifting the breast.
* Knowing your reconstruction options before surgery can help you prepare for a
mastectomy with a more realistic outlook for the future.
5. Types of Breast Reconstruction
The most common implant is a saline-filled implant that has an external silicone shell and is filled with sterile saline (salt water). Silicone gel-filled implants are another option for breast reconstruction, but they are not used as often as they were in the past because of concerns that silicone leakage might cause immune system diseases. However, most of the recent studies show that implants do not increase the risk of immune system problems. Also, alternative breast implants that have different shells and are filled with different materials are being studied, but these are available only in clinical trials.
One-stage immediate breast reconstruction may be done at the same time as your mastectomy. After the general surgeon removes the breast tissue, a plastic surgeon places a breast implant where the breast tissue was removed to form the breast contour.
Two-stage immediate or two-stage delayed reconstruction is done if your skin and chest wall tissues are tight and flat. An implanted tissue expander, like a balloon, is placed beneath the skin and chest muscle. Through a tiny valve beneath the skin, the surgeon injects a salt-water solution at regular intervals to
fill the expander over time. After the skin over the breast area has stretched enough, the expander is usually removed in a second operation, and a permanent implant is put in its place. Some expanders are left in place as the final implant.
There are some important factors for you to think about when deciding to have implants:
* Your implants may not last a lifetime, so you may need more surgery to replace them.
* You can have local complications with breast implants such as rupture, pain, capsular contracture (scar tissue forms around the implant), infection, or an unpleasing cosmetic result. This means that implants may become less attractive over time.
Tissue Flap Procedures
Tissue flap procedures use tissue from your tummy, back, thighs, or buttocks to reconstruct the breast. The 2 most common types of tissue flap surgeries are the TRAM flap (transverse rectus abdominis muscle flap), which uses tissue from the tummy area, and the latissimus dorsi flap, which uses tissue from the upper back. These operations leave 2 surgical sites and scars, both from where the tissue was taken and on the reconstructed breast. The scars fade over time, but they will never go away completely. There can also be complications at the donor sites, such as abdominal hernias and muscle damage or weakness. There can also be differences in the size and shape of the 2 breasts. Because blood vessels are involved, these procedures usually cannot be offered to women with diabetes, connective tissue or vascular disease, or to smokers.
TRAM (transverse rectus abdominis muscle) Flap
The TRAM flap procedure uses tissue and muscle from the lower abdominal wall (tummy tissue). The tissue from this area alone is often enough to create a breast shape, and an implant may not be needed. The skin, fat, blood vessels, and at least 1 of the abdominal muscles are moved from the abdomen to the chest area. This procedure also results in a tightening of the lower abdomen, or a "tummy tuck." There are 2 types of TRAM flaps:
* Pedicle flap involves leaving the flap attached to its original blood supply
and tunneling it under the skin to the breast area.
* Free flap means that the surgeon cuts the flap of skin, fat, blood vessels,
and muscle free from its original location and then attaches the flap to blood
vessels in the chest area. This requires the use of a microscope (microsurgery) to
connect the tiny vessels and takes longer to finish than a pedicle flap. The free
flap is not done as often as the pedicle flap but some doctors think that it can
result in a more natural shape.
Femara(R) helps protect against return of breast cancer even when treatment starts several years after completing tamoxifen therapy
● Post-unblinding analysis of MA-17 trial data provides evidence for potential
benefit of starting Femara up to seven years after finishing tamoxifen
● Femara only member of aromatase inhibitor class with data demonstrating this
potential benefit, as published in Journal of Clinical Oncology
● Half of all breast cancer recurrences occur five or more years after diagnosis
● Separate analysis published in Annals of Oncology affirms significant advantages of Femara when taken after standard tamoxifen therapy
East Hanover, March 10, 2008— Women may reduce the risk of their breast cancer returning by starting treatment with Femara(R) (letrozole tablets) anywhere from one to seven years after finishing tamoxifen therapy, according to a new analysis published today in the Journal of Clinical Oncology(1).
The exploratory analysis of post-unblinding results from the landmark MA-17 trial, led by the National Cancer Institute of Canada Clinical Trials Group, evaluated a subset of women in the original placebo group when the study was unblinded.
The analysis shows that women who started Femara several years after completing the recommended five years of tamoxifen reduced their risk of breast cancer coming back by 63% compared to those who did not start Femara(1). In addition, the risk of cancer spreading to other areas of the body was reduced by 61%. The median period before starting Femara was 31 months.
“The important message for women is that it may never be too late for many breast cancer survivors to do more to protect themselves against the ongoing risk of disease recurrence,” said Paul Goss, M.D., PhD., of the Massachusetts General Hospital in Boston and the lead investigator of MA-17. “These data reinforce the need for women diagnosed with breast cancer to go back to their doctors and continue to discuss ways to reduce their risk of recurrence.”
More than 50% of breast cancer recurrences and deaths occur five or more years after completing tamoxifen treatment(1). Femara is the only drug in the aromatase inhibitor class with data showing its potential to reduce the risk of breast cancer returning even when started several years after initial treatment with tamoxifen.
A separate intent-to-treat analysis of unblinded results from the MA-17 trial, published today in the Annals of Oncology,supports the significant benefit of initiating Femara within three months of completing five years of tamoxifen(2). If women do not have the opportunity to begin Femara treatment within three months of completing tamoxifen, the exploratory analysis published in the Journal of Clinical Oncology indicates they may still benefit from starting Femara up to several years later.
MA-17 was an international, double-blinded, randomized, multi-center Phase III trial to evaluate the effectiveness of Femara versus placebo in breast cancer survivors who had completed five years of tamoxifen treatment. It was led by the National Cancer Institute of Canada Clinical Trials Group at Queens University in Kingston, Ontario with funding from the Canadian Cancer Society and support from Novartis.
The trial was unblinded in 2003 after the first planned interim analysis showed a marked benefit for Femara in reducing the risk of breast cancer recurrence(2). At that time, women in the placebo arm were offered the chance to start treatment with Femara or to continue without additional treatment.
The analysis published in the Journal of Clinical Oncology evaluated the subset of 2,383 women who were in the placebo group when the MA-17 trial was unblinded. Of these women, 1,579 chose to switch to Femara, while 804 chose not to start Femara. The safety analysis was consistent with many other Femara trials in various treatment settings, reinforcing that Femara is well tolerated.
“Novartis has the highest level of commitment to ensuring that women with breast cancer have the knowledge and therapies to reduce their risk of recurrence, whether they were diagnosed yesterday or many years ago,” said Diane Young, M.D., Head of Global Medical Affairs at Novartis Oncology. “Femara offers protection against recurrence throughout several phases of breast cancer treatment in women with hormone-sensitive early breast cancer. These new data add to the body of clinical evidence for Femara.”
The intent-to-treat analysis published in the Annals of Oncology evaluated the outcomes for women assigned to Femara and placebo in the original trial study arms. At a median follow-up of 64 months, Femara significantly reduced the risk of breast cancer recurrence by 32% versus placebo. Femara maintained its significant benefit over placebo, even though more than 60% of women in the placebo group started Femara when the study was unblinded.
Results from this analysis affirm the safety and efficacy of Femara as extended adjuvant therapy (i.e. following the completion of five years of tamoxifen).
Femara(R) (letrozole tablets) is approved for the adjuvant (following surgery) treatment of postmenopausal women with hormone receptor-positive early stage breast cancer. The benefits of Femara in clinical trials are based on 24 months of treatment. Further follow- up will be needed to determine long-term results, safety and efficacy.
Femara is also approved for the extended adjuvant treatment of early stage breast cancer in postmenopausal women who are within three months of completion of five years of tamoxifen therapy. The benefits of Femara in clinical trial are based on 24 months of treatment. Further follow-up will be needed to determine long-term results, including side effects.
In addition, Femara is approved for the treatment ofpostmenopausal women with estrogen receptor-positive or estrogen receptor-unknown breast cancer that has spread to another part of the body (metastatic cancer).
Important Safety Information
You should not take Femara if you are premenopausal. Your doctor should discuss the need for adequate birth control if you have the potential to become pregnant, if you are not sure of your postmenopausal status, or if you recently became postmenopausal. Femara is only indicated in postmenopausal women. Talk to your doctor if you’re allergic to Femara or any of its ingredients. You should not take Femara if you are pregnant as it may cause fetal harm. Some women reported fatigue and dizziness with Femara. Until you know how it affects you, use caution before driving or operating machinery. Some patients taking Femara had an increase in cholesterol. Additional follow-up is needed to determine the risk of bone fracture associated with long-term use of Femara.
In the adjuvant setting, commonly reported side effects are generally mild to moderate. The most common side effects seen with Femara include hot flashes, joint pain, night sweats, weight gain, nausea, tiredness, other heart-related events and bone fractures. Other less commonly reported side effects include vaginal bleeding, blood clots, other cancers, osteoporosis, stroke, heart attack and endometrial cancer.
In the extended adjuvant setting, commonly reported side effects are generally mild to moderate. Commonly reported side effects for Femara include hot flashes, fatigue, joint pain, headache, increase in sweating, swelling due to fluid retention, increase in cholesterol, dizziness, constipation, nausea, cardiovascular ischemic events, muscle pain, osteoporosis, arthritis and bone fracture.
In the metastatic cancer setting, commonly reported side effects are generally mild to moderate and may include bone pain, hot flashes, back pain, nausea, joint pain, shortness of breath, tiredness, coughing, constipation, limb pain, chest pain and headache.
The foregoing release contains forward-looking statements that can be identified by terminology such as “potential”, “may”, “to be”, or similar expressions, or by express or implied discussions regarding potential new indications or labelling for Femara or regarding potential future revenues from Femara. Such forward-looking statements reflect the current views of the Company regarding future events, and involve known and unknown risks, uncertainties and other factors that may cause actual results with Femara to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that Femara will be approved for any additional indications or labelling in any market. Nor can there be any guarantee that Femara will achieve any particular levels of revenue in the future. In particular, management’s expectations regarding Femara could be affected by, among other things, unexpected clinical trial results, including unexpected new clinical data and unexpected additional analysis of existing clinical data; unexpected regulatory actions or delays or government regulation generally; the company’s ability to obtain or maintain patent or other proprietary intellectual property protection; competition in general; government, industry and general public pricing pressures, and other risks and factors referred to in Novartis AG’s current Form 20-F on file with the US Securities and Exchange Commission. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those anticipated, believed, estimated or expected. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.
Novartis Pharmaceuticals Corporation researches, develops, manufactures and markets leading innovative prescription drugs used to treat a number of diseases and conditions, including those in the cardiovascular, metabolic, cancer, organ transplantation, central nervous system, dermatological, gastrointestinal and respiratory areas. The company's mission is to improve people's lives by pioneering novel healthcare solutions.
Located in East Hanover, New Jersey, Novartis Pharmaceuticals Corporation is an affiliate of Novartis AG (NYSE: NVS), a world leader in offering medicines to protect health, cure disease and improve well-being. Our goal is to discover, develop and successfully market innovative products to treat patients, ease suffering and enhance the quality of life. We are strengthening our medicine-based portfolio, which is focused on strategic growth platforms in innovation-driven pharmaceuticals, high-quality and low-cost generics, human vaccines and leading self-medication OTC brands. Novartis is the only company with leadership positions in these areas. In 2006, the Group's businesses achieved net sales of USD 37.0 billion and net income of USD 7.2 billion. Approximately USD 5.4 billion was invested in R&D. Headquartered in Basel, Switzerland, Novartis Group companies employ approximately 100,000 associates and operate in over 140 countries around the world. For more information, please visit
1. Goss PE, Ingle JN, Pater JL, et al. Late extended adjuvant treatment with letrozole improves outcome in women with early-stage breast cancer completing 5 years of tamoxifen. J Clin Oncol. 2008
2. Ingle1 JN, Tu D. Pater JL , et al. Intent-to-treat analysis of the placebo-controlled trial of letrozole for extended adjuvant therapy in early breast cancer: NCIC CTG MA.17. Annals of Oncology. 2008
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Novartis Pharmaceuticals Corporation
Dana Kahn Cooper
Lower cholesterol safely and cheaply
One of the safest and cheapest ways to treat high cholesterol is to change your eating habits. In a nutshell: Eat less saturated and trans fats.
Your goal: no more than 25% to 35% of your total daily calories from fat, keeping your saturated fat intake to less that 7% of total calories and limiting dietary cholesterol to 200 mg or less per day. How can you tell how much and what kind of fat you’re getting? The labels on packaged foods and a calorie counter that includes fat grams are useful tools to help you determine fat calories.
Another tip: saturated fats are solid to semi-solid at room temperature and include the fats in meat, dairy products, and eggs, as well as some vegetable oils, particularly the tropical oils (palm, palm kernel, coconut, and cocoa butter). Most saturated fats stimulate LDL production in the body. Reducing the amount of saturated fat in your diet can lower your LDL.
On the other hand, unsaturated fats, which tend to be liquid at room temperature, include both monounsaturated and polyunsaturated fats. Olive, peanut, sesame, and canola oils are rich in monounsaturated fats, while soybean, corn, cottonseed, safflower, sunflower, and fish oils are high in polyunsaturated fats. In contrast to LDL-raising saturated fats, both monounsaturated fats and polyunsaturated fats have some ability to lower LDL.
Avoid trans fats, which are created when food manufacturers solidify unsaturated liquid oils to create firmer margarines and shortenings. Trans fats have been shown to raise LDL and lower HDL levels in the blood. These fats are a greater risk to heart health than even saturated fats. An expert panel from the Institute of Medicine concluded that trans fats have no known health benefit and that there is no safe level of consumption. Growing data on the hazards of trans fats prompted the FDA to pass a regulation that now requires nutrition labels to include trans fat content.
Monounsaturated fats do not undergo modification, and, when substituted for saturated fats, can help lower LDL cholesterol levels. Replacing saturated fats with monounsaturated fats — for example, using olive oil instead of butter — is one way to improve a wayward lipid profile, as long as you aren’t just adding monounsaturated fats and forgetting to cut back on the saturated fats.
Other diet changes that will help lower cholesterol include eating more fiber, such as that found in oat bran, and increasing your consumption of plant stanols and sterols, which are found in a number of food products. Plant stanol margarines such as Benecol and Take Control are worth trying, since regular use can help lower LDL cholesterol levels.
Research shows that genetic and physiological differences influence how dietary fat affects cholesterol levels. To maximize the benefits of modifying fat intake to lower cholesterol, you should:
1. Determine whether diet changes work for you.
Say you decide to try a lower-fat, lower-cholesterol diet for three to six months, but at the end of the trial period, a blood test shows that your cholesterol levels haven’t budged. You may belong to the nonresponder group and need a different kind of diet, or medication, to control your cholesterol.
2. One size doesn’t fit all.
When a friend or relative tells you how much his or her cholesterol level dropped after trying a particular diet, you may be tempted to try it too. But if after a few months you discover that the diet has no effect, remember, there isn’t a one-size-fits-all recommendation for fat or cholesterol consumption. You may have to try several different diet and exercise approaches to find one that works for you.
Thousands of breast-cancer patients may be getting the wrong treatment because of errors in two laboratory tests widely used to determine which drugs are prescribed.
The tests are used to help determine whether women with invasive breast cancer will receive drugs such as Genentech Inc.'s Herceptin, GlaxoSmithKline PLC's Tykerb and a number of antihormone medications, including the generic tamoxifen and newer treatments such as AstraZeneca PLC's Arimidex and Faslodex.
The pharmaceuticals industry is trying to develop more medicines tailored to the individual characteristics of patients and their diseases. Herceptin, which went on the market in 1998, has been hailed as a breakthrough because it is designed for a certain subset of breast-cancer patients rather than everyone who has the disease.
But recent studies that turned up problems in testing point to a potential snag for such drugs: They depend on accurate lab results.
"We all make the assumption that every test is done well. It turns out it's not a correct assumption," says Lee Newcomer, a cancer doctor who is senior vice president at insurer UnitedHealth Group Inc. Several major private insurers, including UnitedHealth, Aetna Inc. and WellPoint Inc., say they will generally pay for second-opinion breast-cancer tests. However, Dr. Newcomer says that even though UnitedHealth covers a second test, few doctors order them.
In 2007, around 178,000 patients were expected to be diagnosed with invasive breast cancer in the U.S., according to the American Cancer Society. The tests relating to Herceptin and the antihomone drugs are less straightforward than many traditional lab procedures. They require pathologists to make judgment calls after looking at tissue through a microscope, rather than giving simple yes-or-no answers as in a pregnancy test.
One test examines whether a patient's tumor cells have too much of a protein called Her-2. If they do, Herceptin can help by targeting and destroying those cells. The other test checks for the presence of cell proteins that serve as receptors for the hormones estrogen or progesterone. These hormones can help tumors grow, so if the test is positive, doctors often prescribe drugs such as tamoxifen to suppress or block the hormones.
Karen Ivester, a manager at a construction firm in Boca Raton, Fla., was first diagnosed with breast cancer in 2002, when a marble-sized tumor was removed from her right breast. Ms. Ivester, 50 years old, says the local lab found her negative on both tests, meaning she wasn't given Herceptin or hormone therapy. She weathered chemotherapy and radiation.
Last year, after Ms. Ivester had a shooting pain in her ribs during a golf match, doctors found her cancer had returned in the bones of her spine. The new tumor tested positive on the hormone test. More surprisingly, so did her 2002 tumor, which was retested. Her current doctor, Chuck Vogel, says early use of tamoxifen might have headed off or delayed the cancer's return.
"I was absolutely, absolutely furious to know it was wrong, it could have been wrong," Ms. Ivester says. "I lost my first line of defense, and who knows what difference it would have made."
In a study published in 2006 on Her-2 tests -- led by researchers at Genentech -- a large laboratory that is experienced in the procedures reviewed tests performed by local labs around the country. It found that 14% to 16% of those judged positive for Her-2 were actually negative. Of those judged negative, 18% to 23% were in fact positive.
After signs of problems with hormone testing at a lab in Newfoundland, tissue from 763 patients with negative results was retested at a different lab in 2005 and 2006. The new tests concluded that 317 of those were actually positive. Officials at the provincial Eastern Regional Health Authority in Newfoundland, which oversees the lab that had inaccurate tests, said they can't comment on potential causes for the problems because of an ongoing government inquiry and a class-action suit by patients. But they said the authority did pursue the issue.
In another analysis of labs in multiple countries, published online last August in the Journal of Clinical Oncology, 70% of 105 patients scored as negative on the estrogen test were relabeled as positive when the tissue was retested by an experienced lab. The analysis found that positive results were almost always correct.
"If we tried to market pregnancy tests with this rate of inaccuracy, they would be taken off the market," says Allen Gown, chief pathologist of PhenoPath Laboratories, a Seattle lab. "It means there are a lot of women being treated inappropriately." When PhenoPath checked its performance on both breast-cancer tests using different methods, its results were consistent at least 95% of the time, he said.
In the U.S., such concerns could add momentum to efforts by Congress and consumer groups to push for increased oversight over the lab-testing business, which is booming because of factors such as the rise in genetic testing and the aging of the Baby Boom generation. In 2007, overall lab revenues grew 6.5% to around $51.7 billion, according to Washington G-2 Reports, a unit of the Bureau of National Affairs Inc.
"We're going to be looking at a future where diagnostic medicine will be the norm," says Pamela Klein, a vice president at Genentech. She says lab-testing consistency "can still be improved."
While every prescription drug must receive Food and Drug Administration approval, labs have considerable freedom to develop and perform their own tests. The FDA does approve certain testing kits, but labs can tweak the procedures without being required to get a regulatory sign-off on each home-grown method.
Lab-industry officials say this flexibility allows them to quickly translate emerging science into help for patients. They also say labs, which must be inspected every two years by outside examiners, receive strong oversight. "The process and the authority is there and it does work," says Alan Mertz, president of the American Clinical Laboratory Association, a trade group.
"Our system across the industry is a good one, and getting better," said Mara Aspinall, president of the genetics unit at Genzyme Corp., adding she is "very confident" of her own labs' tests.
However, Rolf Ehrnstrom, corporate vice president of research and development at Dako Denmark A/S, a maker of diagnostic tests and equipment manufacturer that sells both Her-2 and hormone-receptor test kits, said that if labs follow the recommendations in testing kits, "you have a much more standardized way of doing it," and the company believes "we need to standardize and make more quality-assurance throughout the labs."
Barry M. Straube, chief medical officer at the U.S. agency that regulates labs, the Centers for Medicare and Medicaid Services, says his agency is examining tougher quality-control requirements. Now labs must pass outside proficiency checks on only 83 types of tests. That list, devised in 1992, doesn't include the breast-cancer tests or dozens of others developed more recently.
"We're considering adding additional tests," Dr. Straube said. The two breast-cancer ones are likely candidates, he says. However, he says that, in general, "oversight is good."
Starting this year, the College of American Pathologists plans to require proficiency checks from the labs it oversees if they want to offer the Her-2 test. The college and the American Society of Clinical Oncology, which issued guidelines for the Her-2 test a year ago, estimated that around 20% of Her-2 testing may be inaccurate.The two groups also plan to look at the other breast-cancer test.
Some industry executives reject the notion that tests are often inaccurate. Joseph Purvis, executive director of clinical research oncology at drug maker AstraZeneca, says he hasn't seen evidence of extensive problems with hormone tests. "I don't think most patients should worry about the quality," he says.
But pathologists and cancer doctors say labs inexperienced in a particular test may not always understand how small variations in procedure can affect results. Reviews of hormone-receptor tests show that findings can change depending on how much the tissue samples are heated and what preservative is used.
Pathologists at Intermountain Healthcare, a hospital group based in Salt Lake City, found that results varied based on the day of the week a patient had surgery -- apparently because tissue that sat in a refrigerator or in preservative over the weekend was different from tissue examined quickly. Intermountain has since changed its procedures.
Hormone-testing methods are "a chaos," says Soonmyung Paik, director of the pathology division at the National Surgical Adjuvant Breast and Bowel Project, a nonprofit clinical research group, because "every lab uses a different method and different criteria to call a case positive."
twelve breast cancer suspects identified by the researchers.
Can our “body burdens” be lightened? Silent Spring researchers advocate reducing as many “preventable” exposures from industrial chemical byproducts as possible. Examples abound: 1,4 dioxane, a contaminant in detergents and shampoos, for example, and fluorescent whitening agents, both have been found to cause breast cancer in animals. The researchers argue that most chemicals used in hair dyes and cosmetics have not been tested for their health effects.
Francesca Lyman is the author of several environmental books, including The Greenhouse Trap and Inside the Dzanga-Sangha Rain Forest. Her work has appeared in The New York Times, The Washington Post, Ms. Magazine, Seattle Metropolitan, MSNBC Online, This Old House, and Horizon Air magazines.
BREAST-SPECIFIC GAMMA IMAGING WITH THE DILON 6800
The Dilon 6800 Gamma Camera enables optimized molecular breast imaging with a high-resolution, small field-of-view detector for image acquisition. The Dilon 6800 overcomes the limitations of a standard gamma camera through a patented detector that produces high contrast images of significantly smaller lesions and helps practitioners determine the presence or absence of cancer. The detector's compact size allows imaging close to the chest wall and in all standard mammographic views for direct correlation to mammograms. An additional benefit is that patients are able to sit comfortably throughout the image acquisition process, rather than lie prone as with standard gamma cameras.
BSGI, as a functional or molecular procedure, images cellular activity while both MRI and Ultrasound image tissue density. Functional imaging allows physicians to see the breast more clearly by accessing a map of cellular metabolism. Certain types of breast tissue may interfere with cancer detection. The need for a complementary diagnostic procedure to mammography is filled by a test that provides for improved sensitivity and specificity such as BSGI.
THE IDEAL DIAGNOSTIC COMPLEMENT TO MAMMOGRAPHY
Mammograms image tissue densities, not cancer activity. BSGI with the Dilon 6800 uses radiotracer uptake to detect cancer independent of tissue density.
With negative predictive values of 99%, and high sensitivity for lesions as small as 3 mm, BSGI with the Dilon 6800 has been integrated into the diagnostic protocol for challenging cases.
“In clinical studies lesions as small as 1mm have been reported by pathology- for both invasive cancer and DCIS. In addition, reports from studies and clinical practice demonstrate a high sensitivity for DCIS and lobular carcinoma.”
BSGI VS. MRI
MRI has shown usefulness as a next-step imaging modality for difficult-to-diagnose cases. Much like x-ray mammography, breast MRI relies on anatomical or structural information, but provides much more detailed images. It is limited however, by its highly variable specificity, which can range from below 37% to 97%. Combined with its high sensitivity, MRI produces a high false positive rate, is an expensive test to administer, is often difficult to schedule and may require multiple days to complete.
The specificity of BSGI/scintimammography has historically been higher than that of breast MRI. In addition, Dr. Petrovitch presented data at the 2005 RSNA showing that in the same patient population BSGI had comparable sensitivity, but higher specificity than breast MRI (High Resolution Molecular Breast Imaging with 99m-MIBI and Magnetic Resonance Imaging in the Assessment of Breast Cancer, 2005). There are also several factors which limit the use of breast MRI in patients.
BSGI VS. ULTRASOUND
Ultrasound is also commonly utilized as a next-step after a questionable mammogram and is good at determining if a suspect mass is solid or fluid-filled. However, ultrasound demonstrates a low specificity that can produce misleading results and indicate biopsy where one may not be needed.
BSGI, as a functional procedure, images cellular activity while both MRI and Ultrasound image tissue density. Functional imaging allows physicians to see the breast more clearly by accessing a map of cellular metabolism. Certain types of breast tissue may interfere with cancer detection. The need for a complementary diagnostic procedure to mammography is filled by a test that provides for improved sensitivity and specificity such as BSGI.
Comparison of Breast Imaging Modalities
-New Technology Can Detect Cancer As Important Additive To Mammography-
Beth Israel Medical Center is the first hospital in New York City to begin using a new tool − Breast-Specific Gamma Imaging (BSGI) − to help identify cancerous breast tissue undetected by mammography.
Clinically proven effective in multiple studies, BSGI technology is particularly useful in serving as a complementary tool for radiologists and breast cancer specialists to detect breast cancer in women with difficult-to-read mammograms, such as those with dense breast tissue, breast implants or scar tissue from previous breast surgery. BSGI also is ideal for high-risk patients, including patients previously diagnosed with breast cancer, atypia and family history of cancer.
By operating on a cellular or molecular level, BSGI is not affected by tissue density and can help detect cancers at very early stages and allow for optimal intervention and treatment. Its ability to accurately detect breast cancer has the potential to significantly reduce the number of unnecessary, invasive biopsies. It also allows for accurate-pre surgical planning to help preserve healthy breast tissue.
“Mammography is still the first-line screening tool for breast cancer, but there are those challenging cases where it raises as many questions as it provides answers,” says Joshua Gross, MD, chief of the division of breast imaging at Beth Israel. “Mammography primarily measures differences in tissue density, but because dense tissue and cancers can have a similar appearance on mammography, it may be difficult to identify cancers (false negative mammograms) and in addition this may also lead to unnecessary biopsies (false positives mammograms).”
BSGI is provided at Beth Israel by the Dilon 6800 camera from Dilon Technologies, LLC. According to Sheldon Feldman, MD, chief of the Appel/Venet Comprehensive Breast Service at Beth Israel, the Dilon 6800 camera and its BSGI technology, which evolved from traditional nuclear medicine imaging (scintimammography), provides a better alternative to magnetic resonance imaging (MRI).
“MRI results can be difficult to interpret and thus has a significant ‘miss’ rate,” said Feldman, who, along with his breast surgeon colleague Susan Boolbol, MD, began offering the Dilon scan to applicable patients earlier this year. “MRI also is expensive, time consuming and a problem for claustrophobic patients. In comparison, BSGI is accurate and very quick to obtain, allowing a patient to receive same-day results. In addition, the Dilon camera requires no breast compression and the portable camera is small enough to fit in any breast center exam room.”
Scintimammography has long shown promise as a diagnostic tool for breast cancer detection, but the limitations of the procedure as performed with standard gamma cameras did not allow for the reliable detection of sub-centimeter lesions or direct correlation to mammograms. Advances in the technology of gamma detectors has led to the progression of a functional breast imaging procedure, BSGI, that is now achieved with anatomic-specific detectors, and in this case, optimized for high resolution breast imaging.
For more information on the use of the Dilon 6800 camera and BSGI technology at Beth Israel Medical Center, please call (800) 753-3229.
Decisions in Women with Early Breast Cancer
Letrozole May Cut Risk of Breast Cancer
Tesmilifene in Addition to Doxorubicin Improves Survival in Advanced Breast Cancer
Doxil (R) Plus Gemzar(R) Active in Metastatic Breast Cancer
Brachytherapy May Be Just As Effective and More Convenient than Whole Breast Radiation for Breast Cancer
According to results recently presented at the 40th annual meeting of the American Society of Clinical Oncology (ASCO), the laboratory test called Oncotype DX(TM), which has already been approved for determining the risk of a recurrence in breast cancer, may also help detect which patients with breast cancer will respond to chemotherapy. Results from Oncotype DX(TM) may help guide patients to the most effective individualized treatment options for their cancer.
Breast cancer is responsible for approximately 40,000 deaths annually in the United States alone. However, if breast cancer is detected early, prior to the spread of cancer, cure rates remain high. Although patients with early breast cancer derive a significant survival benefit overall with the addition of chemotherapy in their treatment regimen, some women may be exposed unnecessarily to chemotherapy, suffering from side effects caused by the treatment while gaining no benefit. By using a test such as Oncotype DX(TM) to determine whether a patient is likely to achieve benefit from chemotherapy and/or is likely to expe- rience a cancer recurrence, physicians can tailor treatment to meet the needs of individual patients. This also allows patients who are not likely to benefit from specific chemotherapy agents to seek other treatment options.
Oncotype DX(TM) is a test that uses breast cancer biopsies, or small tissue samples, to determine whether a patient has breast cancer. The test analyzes the expression of specific genes or clusters of genes of the cancer cells and, through statistical analysis, can provide associations between the expression of one or more genes and specific outcomes of patients, such as risk of a cancer recurrence. Oncotype DX(TM) is presently approved to determine the risk of a distant recurrence in women with node-negative, estrogen receptor-positive breast cancer through the evaluation of 21 genes.
Researchers from Italy recently conducted a study to further evaluate Oncotype DX(TM) and its ability to predict an anti-cancer response to chemotherapy in women with early breast cancer. Previous studies have indicated that a complete disappearance of cancer following treatment upon evaluation under a microscope of a tissue sample, referred to as a pathologic complete response, has been demonstrated to improve cancer-free and overall survival in previous clinical studies. The study included 89 patients who had their biopsy specimens analyzed by Oncotype DX(TM) prior to any treatment. The patients were initially treated with a taxane (Taxotere (R) or paclitaxel), followed by the surgical removal of their cancer, followed by further chemotherapy with a regimen referred to as CMF (cyclophosphamide, methotrexate, 5-fluorouracil), radiation therapy and tamoxifen (Nolvadex (R)) if they were estrogen receptor-positive. Twelve percent of patients achieved a pathologic complete response. The results from Oncotype DX(TM) identified the expression of 86 genes that were associated with the achievement of a pathologic complete response. Expression of these genes tended to be from 3 gene groups: an estrogen receptor group, an immune group and a proliferation group. Patients with a higher expression of genes in the estrogen receptor group had a significantly lower rate of a pathologic complete response, while patients with a high expression of genes from the immune group and proliferation group had a higher rate of a pathologic complete response. Furthermore, when compared to the genes that predict for the risk of a distant recurrence, patients at a higher risk for a recurrence also have significantly higher rates of a pathologic complete response following treatment.
The researchers concluded that Oncotype DX(TM) helps predict a pathologic complete response following chemotherapy for patients with early breast cancer. The fact that patients who are identified to be at a high risk for developing a distant recurrence also tend to achieve pathologic complete responses following therapy led to greater evidence that these patients will achieve improved survival with additional treatment. Further studies will help elucidate exactly which patients will benefit from specified therapeutic approaches, leading the field of oncology into individualized treatment for patients.
Reference: Gianni L, Zambetti M, Clark K, et al. Gene expression profiles of paraffin- embedded core biopsy tissue predict response to chemotherapy in patients with locally advanced breast cancer. Proceedings from the 40th annual meeting of the American Society of Clinical Oncology. 2004. Abstract #501.