Newly diagnosed with metatastic disease: where do we go from here? Rick Michaelson Saint Barnabas Medical Center

A Diagnosis of Advanced Breast Cancer Leads To Many Immediate Questions How am I supposed to deal with this? What about my family? Is this a death sentence? How long do I have to live? How am I going to afford this? A Diagnosis of Advanced Breast Cancer Leads to Many Immediate Questions… As happens with any cancer, a diagnosis of advanced or metastatic breast cancer may lead to many immediate questions that are just as hard to ask as they are to answer. Some of those questions might include… How am I supposed to deal with this diagnosis? What about my family? How will they deal with it? Have I just been given a death sentence? How long do I have to live? How will I ever afford to pay for my treatment? [Patient will not offer answers for these questions.]

Many Challenges The stress of a diagnosis Far-reaching decisions regarding immediate care Family and friends considerations Effect on your job Finding time to think Obtaining reliable information Finding the right healthcare team/ seeking additional opinions Many Challenges… And I think you’d agree that it is logical to expect there to be many challenges as well. A diagnosis is stressful, and it may require some immediate decisions regarding your care. You may have to consider how you’ll tell family and friends about your diagnosis. How will my employer and my ability to work be affected? There may be a lot going on at this time, and it may be difficult for you to concentrate. You may also want to be sure you have found the right healthcare team for you or consider seeking additional opinions.

OUR GOAL

What makes it easier to deal with this….. Knowledge

Knowledge ….about medical issues ….about choosing a treatment team that will provide the best medical care, respect your participation in decision making, and serve as your advocate ….how to find help dealing with the psychosocial issues

Let’s start with medical knowledge Leading websites offering evidence based information www.nci.nih.gov www.cancer.net Advocacy groups’ websites www.breastcancer.org www.mbcn.org www.brainmetsbc.org

Knowledge… about the disease: Basic information Goal of treatment is usually control rather than cure There are more treatment options than for most other types of cancer And the list of options continues to grow Treatment options depend upon the “type” of breast cancer

“Types” of breast cancer Luminal or estrogen receptor positive breast cancers HER2 overexpressing (“positive”) breast cancers “Triple negative” breast cancers Question: should first recurrences be biopsied to verify the primary and to determine the type?

Luminal (ER+) breast cancer Commonest type Breast cancers which depend on estrogen for their survival Identified by the production within the cancer cell of either the estrogen receptor protein (ER) and/or the progesterone receptor (PR)

Treatment options for ER+ disease: Estrogen blockers (endocrine Rx) Rationale – “starve” tumors of estrogen Postmenopausal – estrogen made by adrenals Options Anastrazole or letrozole Exemestane with or without everolimus Fulvestrant Tamoxifen Megestrol Less often (male hormone, hi dose estrogen)

Treatment options for ER+ disease: Estrogen blockers (endocrine Rx) Premenopausal – estrogen made by adrenal glands and ovaries Options Tamoxifen Ovarian suppression or removal Once ovaries removed or suppressed, same options as for postmenopausal women

How are these used? Choice of endocrine therapy depends upon prior endocrine therapies, menopausal status, MD and patient preference Continue one endocrine therapy until it stops working or toxicity Duration of response widely variable If endocrine therapies are no longer effective, consider chemotherapy

ER+ disease: When to switch to chemotherapy Endocrine therapies can take 3 months or more to take effect Consider chemotherapy If disease is “rapidly progressive” and we’re not comfortable waiting 3 months to evaluate benefit If the disease is clearly resistant to endocrine therapy

When to switch to chemotherapy Question I hear a lot at diagnosis – why aren’t you giving me the strongest chemo and endocrine therapy together to knock this thing out?

Why not treat ER+ disease as aggressively as possible? Goal is control No evidence that more aggressive treatment prolongs life any more than less aggressive Endocrine therapy can work just as well as chemotherapy and often with less toxicity Approach: use treatments sequentially

Most effective use of endocrine therapy This is an area where the experience of the medical oncologist is key Some examples….

Endocrine therapy: where the experience of the oncologist counts When to switch therapies Correct use of tumor markers (CA2729, CA 15-3) Evaluating response to endocrine therapy too early Differentiating healing on the bone scan from progressive disease Use of endocrine therapy in the setting of organ metastases (liver, lung) Rare situation where endocrine therapy may be added to chemotherapy Frequency of radiologic evaluations Use of endocrine therapy with reportedly ER- disease

Endocrine therapy - Research Understanding resistance Exploring ways to overcome resistance Blocking other biologic pathways that may be stimulating cell growth One treatment that accomplishes this goal is already on the market (Afinitor) Many others are in development

HER2 positive breast cancer What HER2 positive means Biology of HER2 positive disease More rapidly growing without treatment Tend to respond well to chemotherapy Tend to respond less well to endocrine therapy Options for systemic treatment If ER+, endocrine therapy Chemotherapy (usually with a HER2 blocker) Blockers of the HER2 protein

Commercially available blockers of the HER2 protein Trastuzumab Pertuzumab TDM-1 Lapatinib

Where the experience of the oncologist counts When is it appropriate to use endocrine therapy alone or with a HER2 blocker? If chemo and a HER2 blocker are going to be used – which chemo? Which HER2 blocker? When to stop chemotherapy and continue with a HER2 blocker alone

HER2 positive disease: Some comments Brain metastases a bit more common But tend to be treatable and compatible with significant duration of life Wide variation in responses to treatment Long term response not unusual

HER2 positive disease Probably better understanding of this type than the others Tremendous research Understanding variations in response and resistance to better choose treatment Development of new HER2 blockers Combining HER2 blockers with blockers of other pathways stimulating growth of cells

“Triple negative” breast cancers “Wastebasket” term Right now the only conventional options involve chemotherapy Bad rep – both deserved and undeserved

Triple negative disease: Where the experience of the oncologist counts How to choose the sequence of chemotherapy drugs When to use single agent chemotherapy vs combination How to deal with specific situations Brain metastases Low volume metastatic disease Resecting the primary tumor in the setting of metastatic disease

“Triple negative” breast cancers Tremendous research Identifying subtypes of triple negative disease Identifying abnormal pathways stimulating growth within the cells and developing drugs to interfere with these pathways (targeted therapies) Expectation – very quickly our understanding of triple negative disease will increase and our ability to treat will improve dramatically

Metastatic disease – understanding the literature Most studies use as the primary endpoint “progression free survival” (PFS) PFS is defined as the time from the start of a treatment to progression of disease or death from any cause

Concept of “median” PFS Median – the point at which 50% of people remain without progression and 50% of people have experienced progression Keep in mind: Very few people are at the median Just one measure of benefit of treatment Misses a lot of important data

© 2013 Genentech, Inc. All rights reserved. EMILIA* (TDM4370g) Phase III Progression-Free Survival (PFS) by Independent Review 0.0 0.2 0.4 0.6 0.8 1.0 M Median,Months Events, n Cap + Lap 6.4 304 T-DM1 9.6 265 Stratified HR=0.65 (95% CI, 0.55-0.77) P<0.001 Proportion Progression-Free 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 Time, Months 496 404 310 176 129 73 53 35 25 14 9 8 5 1 495 419 341 236 183 130 101 72 54 44 30 18 3 Cap + Lap T-DM1 Number at risk by independent review: Unstratified HR=0.66 (95% CI, 0.56-0.78, P<0.0001) Cap=capecitabine; Lap=lapatinib Verma S, et al. N Engl J Med 2012;367:1783-1791. [incl. Supplementary Appendix] *Genentech/Roche Sponsored Study © 2013 Genentech, Inc. All rights reserved. 31

Another measure of response - Shrinkage or stabilization of disease Evaluating tumor response Complete remission Partial remission Stable disease Progressive disease “Am I in remission?” Can refer to above definitions “Clinical benefit” – complete + partial + stable disease

How to choose the optimal oncology team? One person’s opinion… Very important that you have on your team an oncologist with expertise in treating people with metastatic breast cancer Two models to ensure that you are getting the best care Have as your primary oncologist a physician whose practice is entirely or almost entirely devoted to breast cancer and who is respected for her/his expertise in your community Have a consulting breast oncology expert work with your own medical oncologist

How to choose the optimal oncology team? How to identify a breast oncology expert Ask your current medical oncologist or your primary care physician/gyn Call a regional office of an advocacy group Go to a National Cancer Institute-designated Comprehensive Cancer Center For your consultant To recommend a breast oncologist in your area

Your team is more than your medical oncologist Making the most of Your office visit Bring a list of your concerns and questions Be concise – even if you need to practice Take notes Take someone with you if you can Get copies of your test results Key Members of Your Healthcare Team Oncologist Other medical specialists Primary Care Physician Nurses/Physician Assistants Social Worker Spiritual counselor Financial counselor Office assistant Talking With Your Healthcare Team… Unfortunately, the amount of time a person can spend talking with their physician or other members of the healthcare team is sometimes limited, and you may be nervous, impatient or even scared.1 So you need to make the best of the time you spend with your healthcare team, making it as useful and informative as possible. Here are some tips and considerations from the National Institutes of Health to help you facilitate those conversations: Jot down and bring a list of your concerns to your appointment.1, 2 Don’t be afraid to speak up. Ask questions.2 Bring a notebook or recorder along and take notes. 1, 2 If possible, bring a trusted friend or family member along with you to the appointment.1, 2 Ask to take a copy of your test results home with you. 2 If your healthcare provider has at-home instructions for you, ask that he or she write them down for you. 1, 2 Make sure to follow any instructions your doctor gave you during the appointment, like how and when to take your medicine.2 Remember that your care is a collaborative effort. [Patient chooses any or all of the approved talking points below to illustrate how to interact with healthcare teams. Always remember these people partner with you to do all they can for your health. They are an integral part of your healthcare. I never hesitate to get in touch with them when I have a concern. Trusting your healthcare team is a crucial part of your care and understanding your treatment. If you are not happy with a member of your healthcare team, it’s okay to ask for a change. Questions are okay! Because of the nature of our disease, treatments are critical. Our healthcare teams are there to answer any questions we may have about possible options, expectations or timelines.] References National Institutes of Health. U.S. National Library of Medicine’s Medline Plus. Bethesda, MD. Available at: http://www.nlm.nih.gov/medlineplus/talkingwithyourdoctor.html. Accessed on January 31, 2013. American Academy of Family Physicians. Leawood, KS. Family Doctor.org. Available at: http://familydoctor.org/familydoctor/en/healthcare-management/working-with-your-doctor/tips-for-talking-to-your- doctor.printerview.all.html. Accessed on January 31, 2013. 35

Your team as your advocate This is about YOU Be respectful of your healthcare professionals BUT try not to be intimidated Recognize that YOU are the priority and the consumer Recognize that you have rights Your rights as a patient Be educated about your condition, options for Rx and HONESTY regarding anticipated outcomes of proposed treatments Ask for a recommendation Have your questions answered Challenge in a respectful way Ask for help in arranging a second opinion Ask for help dealing with emotional or social issues Ask for information about financial concerns

An important issue: Clinical trials As health care workers we encourage participation in clinical trials when appropriate Why consider participation Helps society May offer access to a new effective therapy

Clinical trials: Some questions to consider What is the scientific rationale? What are the specific treatments being investigated? What would be the treatment recommendation if I didn’t participate? What are the possible toxicities? What implications for my quality of life? Required visits, bloodwork, frequency of scans, etc Are any doors closed if I don’t participate now or if I do?

Another important issue: second opinions Why consider Your oncologist may recommend You may feel more comfortable Access to a clinical trial Your oncologist feels there are few options left and you are interested in further therapy

Second opinions Where to go How to find Someone with recognized expertise in breast cancer treatment and access to clinical trials Could be a NCI designated Comprehensive Cancer Center or a regionally recognized expert How to find Ask your oncologist to recommend and help gather records Ask people involved in a local advocacy group Going to an NCI-designated Comprehensive Cancer Center

Newly diagnosed with metastatic disease: Psychosocial issues

Social issues What do I tell my family What do I tell my friends What do I do about work

Dealing with social issues Know that you are not facing this alone Help in dealing with some of these issues Significant other, close friend, close family Social worker at MD office or hospital Specific knowledge about what to tell children, employee rights, etc Work with you in how to address important social issues Support groups

Difficult but practical issues Wills, having someone know where important papers are and what if any personal choices you have Think about medical directive Legacy for loved ones Pictures Experiences Messages for future important events

Some of the “spiritual” issues brought up by this diagnosis What do I want to accomplish in my life How do I want to spend my time and resources How long will I live How do I deal with my family and loved ones if I reach the point of saying “enough” Do I have fears and, if so, how to deal with them Living with uncertainty Of physical discomfort Of death

Facing these and related issues Get information and support from your medical team – be sure to share your questions and concerns Consider frank dialogue with family and friends Seek help from a social worker or other therapist (including meds for anxiety, depression, sleep if indicated) Speak with religious / spiritual leaders Support groups (medical, spiritual) Journaling Quiet meditation Give yourself permission to “let go” and do things you like to enjoy

Some resources on the Web for support and information These are websites known to have reliable, valid information on breast cancer, covering many different topics that may be of interest to patients, caregivers, and even healthcare professionals. You can access all of these resources by going to advancedbreastcancercommunity.org, which is sponsored by Novartis. Cancer Care Living Beyond Breast Cancer Breastcancer.org Metastatic Breast Cancer Network The Breast Cancer Research Foundation Sharsheret Young Survival Coalition METAvivor Research and Support, Inc Cancer Support Community SHARE Sisters Network Inc 47

Summary From the medical viewpoint Breast cancer is very treatable for many people Tremendous research efforts are underway leading to major changes in the way we approach breast cancer and the expectation that outcomes will continue to improve

Closing thought: We can’t control the wind, But we can adjust the sails……

Thank you