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Newly diagnosed with metatastic disease: where do we go from
here?
Rick MichaelsonSaint Barnabas Medical Center
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A Diagnosis of Advanced Breast Cancer Leads To Many Immediate Questions
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• 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?
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Many Challenges
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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
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OUR GOAL
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What makes it easier to deal with this…..
Knowledge
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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
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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
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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
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“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?
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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)
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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)
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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
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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
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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
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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?
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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
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Most effective use of endocrine therapy
• This is an area where the experience of the medical oncologist is key
• Some examples….
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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
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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
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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
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Commercially available blockers of the HER2 protein
• Trastuzumab • Pertuzumab• TDM-1• Lapatinib
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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
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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
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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
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“Triple negative” breast cancers
• “Wastebasket” term• Right now the only conventional options
involve chemotherapy• Bad rep – both deserved and undeserved
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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
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“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
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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
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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
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EMILIA* (TDM4370g) Phase III Progression-Free Survival (PFS) by Independent Review
496 404 310 176 129 73 53 35 25 14 9 8 5 1 0 0495 419 341 236 183 130 101 72 54 44 30 18 9 3 1 0
Cap + Lap
T-DM1
Number at risk by independent review:
M Median,Months Events, nCap + Lap 6.4 304T-DM1 9.6 265
Stratified HR=0.65 (95% CI, 0.55-0.77)P<0.001
0.0
0.2
0.4
0.6
0.8
1.0
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30
Pro
po
rtio
n P
rog
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ion
-Fre
e
Time, Months
Verma S, et al. N Engl J Med 2012;367:1783-1791. [incl. Supplementary Appendix]© 2013 Genentech, Inc. All rights reserved.
*Genentech/Roche Sponsored Study
Unstratified HR=0.66 (95% CI, 0.56-0.78, P<0.0001)Cap=capecitabine; Lap=lapatinib
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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
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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
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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
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Your team is more than your medical oncologist
– 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
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Making the most of Your office visit
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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
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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
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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?
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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
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Second opinions
• Where to go– 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
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Newly diagnosed with metastatic disease: Psychosocial issues
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Social issues
• What do I tell my family• What do I tell my friends• What do I do about work
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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
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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
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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
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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
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Some resources on the Web for support and information
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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
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Closing thought:We can’t control the wind,
But we can adjust the sails……
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Thank you