Excerpts from the Audio Program

Psychosocial issues in younger women with breast cancer

Effect of breast cancer treatment on family planning and work

Fertility is a very common concern. For women who are of childbearing age and have never had children, this is one of the most difficult issues they face. Depending on the type of treatment they undergo, many women with breast cancer can have children later on. For some women, however, it is also difficult to contend with the idea that treatment may induce menopause and prevent them from ever having children.

Work is also a concern for younger patients. Many women think they can fit breast cancer into their busy schedules and not take some time out. Those patients often “crash” about three or six months into their treatment. I had one woman who had recently been diagnosed and said, “I have to go on this trip and this trip and this trip.” I said, “This is your key chance to take care of this disease. You need to take care of yourself.”

Sometimes women do not appreciate that breast cancer can be a life-threatening disease. Some will disassociate themselves from what is happening and not take ownership of it. This is not typical of everybody, but it does happen with some patients.

— Jean M Lynn, MPH, RN, OCN

Talking to children about a diagnosis of breast cancer

I always try to tell patients to keep conversations with their children simple, but honest. I believe it is best to provide details in small doses, in order to allow a child to process the information. When the child is ready, he or she will ask more questions.

A patient can start by saying, “Mommy has something in her breast that doesn’t belong there and the doctors are going to take it out.” Then the child can come back and say, “How did it get there?” or, “How long has it been there?”

I don’t think that a patient should hide what is happening. She should try to explain to her children, without scaring them, that she may look different, lose her hair or not have as much energy as she had in the past. It is important to make sure that children don’t feel threatened, are confident that they are going to be taken care of, and believe that their mother is going to receive the help she needs.

It’s also important to recognize that what is good for a four-year-old child is not appropriate for a teenager. Many teenagers are just discovering their sexuality, and a very different connotation may be associated with their mothers having something wrong with their breasts.

Studies have shown that many teenagers will be angry and will act out more because an alteration in their general lifestyle has occurred, and life isn’t as copasetic as it previously was. Some teenagers will drink alcohol or use drugs, so parents should be aware and try to manage their children’s anger and insecurity.

— Jean M Lynn, MPH, RN, OCN

Metastatic breast cancer as a chronic disease

We currently do not have curative therapy for patients diagnosed with Stage IV breast cancer. Ten years ago, we were using high-dose chemotherapy with bone marrow transplant support to try to achieve a cure. Unfortunately, we were not able to reach that goal, and we caused some patients significant toxicity.

That experience has encouraged us to change to a chronic disease model, and now we are focused on patients living with their disease — keeping the cancer under control and maintaining quality of life.

I think most patients understand the implications of Stage IV disease and are concerned about how sick they are going to be with treatment. As a result, the discussion usually transitions to how we are going to keep the disease under control. Many women ask, “How much time do I have?” Fortunately, with the changes that have occurred in the last two decades, for many patients we can feel comfortable saying that we’re not talking about weeks or months, but usually years.

— Nicholas J Robert, MD

Managing stress associated with caring for young patients with metastatic breast cancer

On many days an oncology nurse can feel overwhelmed. I have a different take on things. Whatever happens from the time I walk in that door to the time I walk out, if it’s within my ability to solve it, I’ll solve it. If it’s not, then I’ll try to determine someone who I think can. But for me, coping is just telling myself that I’m going to do the best I can.

I can only do so much, but I’ll give it my all. And when I walk out that door, I want to know I did everything I could. My mom died of colon cancer when I was 13 years old. That experience was life altering. She was a nurse and knew at the time of diagnosis what to expect.

I know what it’s like to lose someone you love. My friend’s mother was also a nurse at that time, and she became my mother’s primary nurse in the hospital. There was nothing that she didn’t do for my mom, so I always try to think back and do the same thing as if this were my relative. You always want to go the extra mile and that’s what I do every day. When I leave, I’m satisfied, and it helps me come back the next day and do it again.

—Heather C Morgan, RN

Role of the oncology nurse

Nurse educators are critical to preparing patients for their treatment and helping them understand the trajectory of their disease. Whenever I teach patients, I always tell them that they will read or hear about many topics that they won’t necessarily understand.

I encourage them to write down everything they are uncertain of, because I believe there is no reason for a patient not to know everything about this disease. We are here to provide patients that extra level of education, so that they do not fear the unknown. I believe that knowing what is going to happen and why, is really half the battle of entering the world of breast surgery and chemotherapy.

— Jean M Lynn, MPH, RN, OCN

It is never easy to watch young women die from breast cancer, but I think oncology nursing has been one of the most rewarding experiences in my life. I cannot imagine a career that would give me as much fulfillment. Being able to hold a patient’s hand, help them through the diagnosis, support them, advocate for them, and make sure that they have the best quality of life for whatever time that they have left is truly rewarding.

However, it’s also important to disassociate when you leave work. If you take work home with you, it may become overwhelming and you will never be effective at this job. When I was 25 years old, I was taking care of ovarian cancer patients and they were very, very sick. I became very close to them, and I almost had to take a break from oncology because I was not separating myself from my work. You need to have a life away from the job. For me, having children and other interests outside of nursing has allowed me to have balance and be more effective as an oncology nurse.

— Jean M Lynn, MPH, RN, OCN

Impact of breast cancer on relationships and dating

Many women face sexuality issues and their body images are often altered by a surgical scar, a mastectomy or hair loss. Many patients feel less sexually attractive to their partners. I have been a part of many discussions in support groups about how and when a woman should tell her partner that she has breast cancer, a reconstructed breast or metastatic disease. I don’t think we have a clear answer to any of these.

I think it depends on the relationship and the two people involved in it. Many women are afraid to tell their partners about the disease because they fear losing the man. If the relationship is good, I believe most men will surprise women and stick around.

We have seen this happen many times. Many relationships — especially marriages — grow closer because the partner is really there. On the other hand, if the relationship wasn’t very good, women will often say, “I may have a limited amount of time and I’m not going to stick around here anymore, because this has never been a fulfilling relationship.”

— Jean M Lynn, MPH, RN, OCN

Advances in adjuvant hormonal therapy

ATAC adjuvant trial

In postmenopausal women, the ATAC adjuvant trial compared anastrozole to tamoxifen and the combination of anastrozole and tamoxifen. Surprisingly, the trial demonstrated a benefit for adjuvant anastrozole alone, but not in combination with tamoxifen. Patients treated with adjuvant anastrozole not only had a reduction in distant breast cancer recurrence, but also a reduction in the incidence of second breast cancers. The toxicity profile was also better for anastrozole than for tamoxifen.

— Nicholas J Robert, MD

Adverse events in the ATAC trial

Tamoxifen has an effect on the uterine wall but anastrozole does not. Women treated with anastrozole had a statistically significant lower incidence of vaginal bleeding. Women with vaginal bleeding require a panoply of tests, including transvaginal ultrasounds and uterine biopsies. Not only do women on anastrozole have fewer symptoms but also fewer interventions. In the United States, the average postmenopausal woman has a 0.1 to 0.2 percent annual risk of developing endometrial cancer. Women on tamoxifen, however, have a 0.4 percent annual risk, and women on anastrozole have about a 0.1 percent annual risk.

Women on anastrozole also have a lower incidence of hot flashes and vaginal discharge. On the other hand, they have more vaginal dryness and dyspareunia. The women on anastrozole also have an increased incidence of musculoskeletal achiness. Surprisingly, musculoskeletal achiness also occurred in the women on tamoxifen. The achiness is fleeting, migratory and annoying. It tends to respond to the nonsteroidal anti-inflammatory drugs (NSAIDs); however, I don’t like using NSAIDs long term.

— Gershon Locker, MD

Bone subprotocol of the ATAC trial

Significant bone loss was reported in women receiving anastrozole compared to tamoxifen. Compared to the women treated with tamoxifen, the overall risk of fractures was increased 1.6-fold for the women treated with anastrozole. The increased risk appeared to be maximal at the two-year point, where it was about two-fold; it then leveled off to about a 1.5- to 1.6-fold increased risk.

More osteoporotic fractures (eg, vertebral, hip and colles) occurred in women receiving anastrozole. Interestingly, the excess osteoporotic fractures were vertebral and colles, not hip fractures. Perhaps it takes longer for the hip to demineralize and to have an increased risk of fracture. A similar increase in nonosteoporotic fractures (ie, long bones) was also seen, but that may be coincidental because those types of fractures occur traumatically rather than by virtue of bone loss.

— Gershon Locker, MD

Selecting adjuvant hormonal therapy

Various studies evaluating aromatase inhibitors in the adjuvant setting provide sufficient data to warrant that all medical oncologists discuss the use of an adjuvant aromatase inhibitor with postmenopausal women who have hormone receptor-positive tumors. My preference would be to use adjuvant anastrozole up front. Others might use an aromatase inhibitor later on.

Long-term data from the ATAC trial, and long-term toxicity data in the metastatic setting, indicate that the aromatase inhibitors are superior to tamoxifen, but if for some reason a woman does not want anastrozole, I would be willing to start her on adjuvant tamoxifen and then consider switching after two or three years.

If the woman’s baseline bone mineral density is normal, I use adjuvant anastrozole and repeat the bone mineral density to decide when a bisphosphonate is needed. In a woman with osteopenia and a high risk of recurrence, I would start a bisphosphonate and treat her with adjuvant anastrozole. If the patient has severe osteoporosis, I may start her on tamoxifen, and consider switching her to anastrozole later on.

If the woman were at high risk for deep vein thrombosis or any of the other complications associated with tamoxifen, I would treat her with anastrozole. For example, a woman with severe osteoporosis and a history of pulmonary embolism would receive adjuvant anastrozole and a bisphosphonate. I believe the risk of a lethal pulmonary embolism from tamoxifen far exceeds the risk of a fracture from anastrozole.

— Gershon Locker, MD

Role of the aromatase inhibitors following adjuvant tamoxifen

We have data for adjuvant anastrozole up front in postmenopausal patients, exemestane and anastrozole following two to three years of adjuvant tamoxifen, and letrozole following five years of adjuvant tamoxifen. I believe each drug has its own niche.

I strongly urge women with node-positive disease who are completing five years of adjuvant tamoxifen to continue their adjuvant therapy with letrozole. I don’t know how long to continue the therapy because the MA17 trial was stopped early; however, I would probably treat them for another two or three years because that was the median duration of therapy for the women enrolled in the study at the time it was stopped.

For a woman with node-negative disease who has completed five years of adjuvant tamoxifen, I discuss the pros and cons of continuing therapy with letrozole and I try to individualize the recommendation.

— Gershon Locker, MD

Counseling women about hormonal therapy side effects

Premenopausal women treated with ovarian suppression have hot flashes, vaginal dryness and a reduced libido. Because they will also have an increased risk of osteoporosis, they require an adequate calcium intake and a DEXA scan at least once every two to three years.

Postmenopausal women should be educated about similar issues. Because they have already been through menopause, postmenopausal patients may not have the severe side effects of hot flashes, insomnia, vaginal dryness, etcetera.

Muscle and joint pains are a big complaint for the patients on the steroidal and nonsteroidal aromatase inhibitors. The involved joints are usually the hips and knees, and sometimes the elbows and shoulders. We must educate patients about the use of NSAIDs to help with those particular side effects.

The side effects associated with tamoxifen are different for pre- and postmenopausal women. The most significant side effects are hot flashes, vaginal discharge and vaginal dryness. If the women are premenopausal and receiving an LHRH agonist with tamoxifen, those symptoms will obviously be more pronounced.

Patients on tamoxifen are also at risk for cataracts and blood clots. For postmenopausal women, tamoxifen has a better profile in terms of osteoporosis. Endometrial cancer is always an issue with tamoxifen, and we tell patients to have pelvic exams and pap smears.

The issue of weight gain associated with tamoxifen is controversial. Most of the women who complain of weight gain have gained some weight on chemotherapy. Some patients say that tamoxifen causes weight gain; however, studies have shown that it does not.

These treatments are also associated with fatigue, and I encourage my patients to walk for half an hour every day to improve their energy level to decrease the fatigue. Nursing research demonstrates that patients who exercise while undergoing treatment have less fatigue, insomnia and stress.

— Jean M Lynn, MPH, RN, OCN

Sequencing hormonal therapies in women with metastatic disease

Parenteral versus oral administration of endocrine therapy

Fulvestrant works by inhibiting and destroying the estrogen receptor, and it’s believed to be more of a pure antagonist than tamoxifen, which can produce some estrogen-like effects. Fulvestrant is given intramuscularly, which has not been a problem in terms of patient acceptance or compliance and is actually advantageous for patients who can’t afford an oral endocrine agent. Oral therapy reduces the number of office visits for the patient; however, patients with metastatic disease who are on bisphosphonates are already coming into the office regularly.

A pill is probably preferable for most patients, but I believe as many as 40 percent of patients would prefer an injection, assuming efficacy and side effects were the same. However, when offering patients a choice between oral and parenteral administration, physicians may be biased. We are more accustomed to choosing between an oral agent versus chemotherapy, which is an easy decision that has nothing to do with the route of administration, but rather the unfavorable side-effect profile of chemotherapy.

— Nicholas J Robert, MD

One benefit of fulvestrant, especially with older patients who have Medicare as their primary insurance, is that it’s covered because it’s administered by injection in the office. For many women, the cost of oral tamoxifen or aromatase inhibitors is an issue. I don’t believe the actual route of administration strongly influences a patient’s decision-making — many of them are used to injections and fulvestrant is not a particularly painful injection.

However, unless they are already returning for another therapy, additional visits for treatment matter because most patients try to minimize the number of visits. Another problem with oral medications is that patients are anxious about missing a treatment and how it will affect their well-being, so the possibility of forgetting a pill or needing a refill when they are about to go out of town concerns some patients.

— Ann Marie Bamford, RN, MSN

Administration and tolerability of fulvestrant

In our practice, fulvestrant is generally administered as a 5-cc intramuscular injection, which patients find less uncomfortable than the subcutaneous injections used to treat chemotherapy-related anemia. With fulvestrant, the injection doesn’t cause pain or burning and patients tolerate it well. Also, in my experience, patients do not call the office complaining of hot flashes or other problems while on fulvestrant.

— Ann Marie Bamford, RN, MSN

Fulvestrant is an injectable hormonal therapy that basically blocks, binds and degrades the estrogen receptor and, hopefully, eliminates any trace of estrogen in the body. The drug itself is well tolerated, but many nurses are anxious about the volume of the injection. We generally give one 5-cc injection rather than splitting the dose between two injections, but in very thin or emaciated patients, you have to use your clinical judgment. The drug is administered slowly because it has a castor oil base, and it’s injected at a 90 degree angle. I recommend injecting it in a z-track, which delivers the drug directly into the muscle while reducing seepage into the subcutaneous tissue.

I find patients like to see a nurse once a month. It gives them an opportunity to ask questions, discuss side effects, talk about other issues that are important in their lives, and they feel more closely monitored. It also provides the nurse the opportunity to discuss with the patient and her family the goal of therapy, which in the metastatic setting is palliative, not curative.

Patients have a relatively good quality of life while on fulvestrant. I have patients who have been stable on this agent for 15 to 18 months. I’ve seen significant responses to fulvestrant — bone pain disappeared and liver metastases, tumor burden and need for pain medication reduced — and the patient’s quality of life is significantly improved.

— Jean M Lynn, MPH, RN, OCN

Side effects of fulvestrant versus other endocrine therapies

Fulvestrant is well tolerated and I believe it has fewer hormonal side effects than tamoxifen or the aromatase inhibitors — specifically fewer hot flashes and other gynecologic symptoms. The injections are well tolerated but they can be inconvenient. I haven’t found compliance with oral medications to be an issue, but reimbursement is easier with fulvestrant. I believe the important issues that support the use of fulvestrant are its efficacy and safety profile.

— Gershon Locker, MD

Duration of response with fulvestrant

In the third-line setting for patients with metastatic disease, objective responses are unexpected and stable disease is desirable. We’ve had patients remain stable on fulvestrant for a couple of years. In the trial comparing fulvestrant to anastrozole, a subset analysis suggests that longer durations of response occur with fulvestrant. In the patients who responded with objective tumor shrinkage, which is a minority of patients, those on fulvestrant had prolonged stable disease and symptomatic improvement. I believe the major benefits of fulvestrant are that it has a good safety profile, is well tolerated and works even in the third-line setting.

— Gershon Locker, MD

Sequence of endocrine therapy in metastatic disease

Clinically, fulvestrant is generally used in the third-line setting because, in the pre- ATAC era, most of the women with metastatic disease already received adjuvant tamoxifen and an aromatase inhibitor after progression. The crossover studies argue that any one of the three classes of drugs — selective estrogen receptor modulators (SERM), aromatase inhibitors or the estrogen receptor downregulator fulvestrant — can be used first line and then cross over to the others. In the fulvestrant studies, response to aromatase inhibitors after fulvestrant in women who were aromatase inhibitor-naïve definitely occurred. I believe we can sequence these agents either way and given the duration-of-response data with fulvestrant, one might prefer it up front.

— Gershon Locker, MD

EFECT Trial

This study randomly assigns postmenopausal women with ER-positive metastatic breast cancer to either the steroidal aromatase inhibitor exemestane or fulvestrant. Both drugs have been shown in Phase II trials to be efficacious. We just don’t know which one is going to be better. We know that fulvestrant was as good, if not a little bit better, than the nonsteroidal aromatase inhibitor anastrozole. So now we’re comparing fulvestrant to exemestane, which is a steroidal aromatase inhibitor that inactivates the aromatase enzyme. The nonsteroidal aromatase inhibitors, like anastrozole and letrozole, inhibit the aromatase enzyme. Fulvestrant blocks, binds and degrades the estrogen receptor. Both drugs have the potential to be effective, and this trial will determine which one is better.

— Jean Lynn, MPH, RN, OCN

Trastuzumab in the treatment of HER2-positive disease

Mechanism of action of trastuzumab

Multiple mechanisms have been proposed. Trastuzumab binds with high affinity to the extracellular domain of the HER2 receptor, and this decreases the amount of signal transduction and cell growth. Trastuzumab is also capable of potentiating the efficacy of chemotherapy through multiple mechanisms. It blocks DNA repair, which is synergistic with DNA damaging agents, and it promotes apoptosis or cell death for agents like the taxanes that induce apoptosis.

— Mark D Pegram, MD

Use of trastuzumab in combination with chemotherapy

When I am treating a patient with HER2-positive metastatic disease, I consider using single-agent trastuzumab. I evaluate the pace and extent of the disease and the patient’s symptomatic condition. The more concerned I am about the patient’s tumor burden, the greater the likelihood that I will add chemotherapy to trastuzumab. What is nice about this approach is that you don’t have to keep the patient on chemotherapy long term because you have another way to control the disease. In these cases I give chemotherapy and trastuzumab for four to six months, stop the chemotherapy and continue the trastuzumab. I have had good control with this approach.

— Nicholas J Robert, MD

A number of highly active regimens can be considered for first-line therapy for the patient with HER2-positive disease. This is important because we are using many drugs in the adjuvant setting. Agents that were once considered to be salvage regimens are now being moved up front. Vinorelbine/trastuzumab is a classic example. We have observed wonderful responses with that regimen, and its efficacy was confirmed by a multicenter trial.

In deciding which agent to use in combination with trastuzumab, I evaluate the clinical setting and apply an evidence-based approach. If the patient relapses not long after initial adjuvant therapy, these newer combinations are attractive. This is an exciting time because new Phase II data exist with so many innovative trastuzumab containing combinations that fortunately our patients have a lot to choose from.

— Mark D Pegram, MD

Tailoring treatment with trastuzumab to match chemotherapy schedule

The schedule of trastuzumab often depends on whether the patient is receiving chemotherapy or not. If the patient is on a weekly chemotherapeutic regimen, we will often give the trastuzumab at the same time. For patients who are off chemotherapy, I regularly administer trastuzumab every three weeks. If the patient has particular problems we may use a different regimen altogether, but that is rather uncommon.

— Nicholas J Robert, MD

I always explain to a patient beginning treatment with trastuzumab that the initial infusion will be a larger loading dose, and the potential exists to have a hypersensitivity reaction. We ask patients to remain at the office for a couple of hours of observation because these reactions generally happen an hour or so later. I also explain that trastuzumab is an agent we give on a continuing basis.

When I first started seeing patients on trastuzumab, everyone was receiving it on a weekly basis; however, an issue arose when patients wanted to go on vacation. We really did not know what to do so we started by giving patients a double dose and letting them skip a week. We would give the infusion over a longer period of time and it seemed to be well tolerated.

Now we have progressed to the point that we are adjusting the trastuzumab schedule to fit the patient’s chemotherapy regimen. If a patient receives three weeks of chemotherapy and has a week of rest, we will give her weekly trastuzumab for the first two weeks and then a double dose on the third week. This is a big quality-of-life improvement that allows patients to go places and do things rather than being tied down by additional treatment.

— Ann Marie Bamford, RN, MSN

Quality control with HER2 testing

The fluorescence in situ hybridization (FISH) assay is a DNA-based HER2 assay. DNA has a stable structure as a macromolecule. If you examine DNA extracted from 3,000-year-old mummies in Egypt, you can still achieve polymerase chain reactions (PCR) with it. Even after the fixation of a surgical tumor specimen in formaldehyde and storage in paraffin wax, you can still use the DNA from the sample to obtain clear and quantitative signals with the FISH assay.

On the other hand, HER2 is a complex, highly folded and unstable protein. As soon as you drop formaldehyde on a tumor, the HER2 protein completely denatures and unfolds. All of the antibodies that try to detect that protein are no longer capable of binding to the target. Unfortunately, that results in many false positives with many of the commercially available HER2 immunohistochemistry (IHC) assays. This means that IHC results for formalin-fixed, paraffin-embedded tumors are just not reliable.

The experience of the North American cooperative groups in the adjuvant trastuzumab trials has shown this to be the case. Reports from both the NSABP and Intergroup trials showed that the concordance between community-based IHC results and central-reviewed IHC results was unacceptable, and I really believe that IHC is not going to be with us for the long haul.

— Mark D Pegram, MD

Clinical trials evaluating adjuvant trastuzumab

The role of trastuzumab in the adjuvant setting is currently being explored in several clinical trials. Our group and others are actively enrolling patients in these clinical trials, and we all anxiously await their results. At this point, we have to remember that trastuzumab has a potential for benefit, but it also has a potential to do harm. Already, in one of the studies, it has been recognized that the rate of congestive heart failure with trastuzumab is approximately three and a half percent; therefore, it is imperative that we determine not only how much trastuzumab helps but also whether or not any harm is associated with using it.

— Nicholas J Robert, MD

Tolerability of trastuzumab

Trastuzumab is well tolerated, and compliance and acceptance is high. Initially, patients can experience fever and chills, but with subsequent treatments, those side effects are not observed. Trastuzumab is not associated with hair loss, nausea, vomiting or problems with blood counts. It is given intravenously, which means that patients need to come into the office or clinic for intravenous infusions, but these can be administered in approximately one hour. Evidence now demonstrates that trastuzumab can be administered every three weeks, making it a relatively convenient drug.

— Nicholas J Robert, MD