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

3. 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.]

4. 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.

5. OUR GOAL

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

7. 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

8. Let’s start with medical knowledge
Leading websites offering evidence based information
Advocacy groups’ websites

9. 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

10. “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?

11. 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)

12. 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)

13. 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

14. 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

15. 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

16. 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?

17. 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

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

19. 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

20. 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

21. 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

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

23. 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

24. 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

25. 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

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

27. 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

28. “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

29. 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

30. 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

31. © 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, )
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, , P<0.0001)
Cap=capecitabine; Lap=lapatinib
Verma S, et al. N Engl J Med 2012;367: [incl. Supplementary Appendix]
*Genentech/Roche Sponsored Study
© 2013 Genentech, Inc. All rights reserved. 31

32. 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

33. 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

34. 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

35. 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: Accessed on January 31, 2013.
American Academy of Family Physicians. Leawood, KS. Family Doctor.org. Available at: doctor.printerview.all.html. Accessed on January 31, 2013. 35

36. 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

37. 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

38. 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?

39. 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

40. 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

41. Newly diagnosed with metastatic disease: Psychosocial issues

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

43. 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

44. 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

45. 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

46. 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

47. 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

48. 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

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

50. Thank you