Download Slide 1 - National DPAC

Update on Common
Malignancies in Women:
Breast and Cervical Cancers
DINA DUMERCY, PHARM.D., BCOP
ONCOLOGY IT PHARMACIST
MEMORIAL HEALTHCARE SYSTEM
MIRAMAR, FLORIDA
Disclosures
 Dina Dumercy, Pharm.D. declares no conflicts of
interest or financial interests in any product or
service mentioned in this activity, including grants,
employment, gifts, stock holdings, and honoraria
Objectives
Upon completion of this program, the participant
will be able to:
 Describe the prevalence and diagnosis of breast
and cervical cancers
 Recommend the latest screening
recommendations for breast and cervical
cancers
 Review guidelines for appropriate selection of
therapy
 Describe strategies that pharmacists can use to
enhance patient compliance to therapy
Cancer Statistics
 About 1, 529, 560 new cancer cases are expected to
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be diagnosed
569,490Americans are expected to die of cancer
(more than 1,500 people a day)
Cancer is the second most common cause of death in
the US, exceeded only by heart disease
In the US cancer accounts for nearly 1 of every 4
deaths
African Americans are more likely to develop and die
from cancer than any other racial group
American Cancer Society. Cancer Facts and Figures, 2010. Atlanta: American Cancer Society; 2010.
Estimated New Cases and Death By Sex
Commonly Asked Questions
 What is cancer?
 Is there anything to prevent cancer?
 What is the best treatment for cancer?
 Where can I get more information on the guidelines
for treatment?
 What are the risk factors for developing cancer?
 They tell me I have cancer, what should I do?
What is cancer?
 A group of diseases characterized by uncontrolled
growth of abnormal cells, when this spread or growth
is uncontrolled it may lead to death.
 A multistep process in which an accumulation of
genetic events with a single cell line leads to a
progressively dysplastic cellular appearance,
deregulated cell growth and finally evident disease.
Carcinogenesis
http://www.dkfz.de/en/tox/images/scheme-cancer-prevention.jpg (Permission requested)
What are the risk factors for Cancer?
 Genetics
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Family History
Genetic testing
 Lifestyle
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Tobacco
Exercise
Diet
 Environmental
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Radiation
Asbestos
 Personal History
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Cancer
Pre-malignant disease
Infections
Medications
Breast Cancer
•2 0 7 , 0 9 0 N E W C A S E S O F I N V A S I V E B R E A S T
CANCER (IBC) WERE EXPECTED TO OCCUR IN
WOMEN IN THE US DURING 2010
•A B O U T 1 , 9 7 0 N E W C A S E S A R E E X P E C T E D I N
MEN
•5 4 , 0 1 0 N E W C A S E S O F I N S I T U B R E A S T
CANCERS ARE EXPECTED (85% DUCTAL
CARCINOMA IN SITU)
•L I F E T I M E R I S K O F D E V E L O P I N G B R E A S T
CANCER IS 12.3% (1 IN 8 WOMEN)
Risk Factors
 Female gender
 Family history
 Increasing age
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 Early menarche
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 Late Menopause
 Older age at first
childbirth
 Hormone replacement
therapy
 Chest wall irradiation
 Benign proliferative
breast disease

Early onset breast cancer
Family with known
mutation
2 or more 1st degree
relatives or 1 with Dx
before 50 yrs of age
 Genetic mutations (i.e..
BRCA1 or 2, PTEN, p53)
 Ovarian/ Fallopian/
peritoneal cancers
Normal Risk Breast Cancer Screening
NCCN Guidelines Version 1.2011 Breast cancer Screening and Diagnosis
Breast Cancer Increased Risk
NCCN Guidelines Version 1.2011 Breast cancer Screening and Diagnosis
Increased Risk Breast Cancer Screening
NCCN Guidelines Version 1.2011 Breast cancer Screening and Diagnosis
Breast Cancer Risk Assessment
 Patient with moderate or high risk factors should be
seen for genetics counseling
 Risk reduction counseling should occur for all
women with high lifetime risk
 Surgical risk reduction strategies generally reserved
for patients with strongly predisposing gene
mutation
 Risk Reduction agents Tamoxifen and Raloxifene are
options after a discussion on the relative risk
reduction, adverse reactions and benefits
Risk Reduction agents
Trials
Outcome
NSABP P-1
(BCPT)
(n=13,388)
Placebo vs.
Tamoxifen 20 mg/d
x5y
•Reduce risk of IBC by 49% (P<0.00001)
•Risk of IBC reduced by 56% and 86% in
LCIS and atypical hyperplasia, respectively
CORE
(n=5,213)
Placebo vs.
Raloxifene 60 or 120
mg
•Reduce risk of IBC by 66% @ 4 yrs
•Risk of IBC and ER+ IBC reduced by 66%
and 76%, respectively @ 8 yrs
NSABP P-2 Tamoxifen 20 mg vs.
(STAR)
Raloxifene 60mg
(n=19,747) daily for 5 years
•@8 years follow-up Raloxifene 76% is as
effective as Tamoxifen in reducing IBC risk
•Raloxifene is as effective as Tamoxifen in
reducing risk in Atypical hyperplasia
Fisher, B. CA Cancer J Clin 1999;49(3):159-77. Vogel, VG. JAMA 2006;295(23):2727-41.
Breast Cancer Work-up
 History and Physical
 Diagnostic bilateral mammogram +/- ultrasound
 Pathology review (ER/ PR/ HER2 status/ Histology,
etc)
 MRI (if necessary)
 Additional studies based on symptoms and stage
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Bone scans
CT/ PET/ Chest Imaging/ MRI
Breast Cancer Staging
Breast Cancer Histopathologic Types
Treatment Approach
 Surgery
 Radiation
 Chemotherapy
 Biological therapy
 Endocrine therapy
 Treatment of Breast cancer is determined by
prognostic and predictive factors and patient
preference

Histology, TNM status, PS, pathology, age, comorbidities, menopausal status
Adjuvant Treatment
ER/ PR (+) HER2 (-)
Adjuvant Endocrine +/- Adjuvant
Chemotherapy
1, 2
ER/ PR(+) HER2 (+)
Adjuvant Endocrine +/- Adjuvant
Chemotherapy + Trastuzumab
1
ER/ PR (-)/ HER2 (+)
Adjuvant chemotherapy +
Trastuzumab
ER/PR (-)/ HER2 (-)
Adjuvant chemotherapy
1
3
Endocrine Tx and Chemo given sequentially with Chemo given first
2 21 Gene RT-PCR Assay to determine recurrence risk score to assist in
treatment decision, must be done within interval between surgery and start of
treatment
3 Triple negative breast cancer
Adjuvant Endocrine Therapy
Adjuvant chemotherapy
 AC-> Paclitaxel weekly or Docetaxel Q3W +/- T
 Dose dense AC -> Paclitaxel Q2W
 TAC
 FEC/ CEF-> Docetaxel Q3W or Paclitaxel weekly+/- T
 TC
 EC
 CMF
 FAC/ CAF
 TCH (Docetaxel/ Carboplatin/ Trastuzumab)
CEF vs. EC/T vs. AC/T
 N= 2104
 Endpoints: RFS, OS, toxicity as assessed by the NCI
Common Toxicity Criteria and QOL
 Interim analysis for recurrence-free survival (RFS) at
median follow-up of 30.4 mos
Burnell, M. et. al. J Clin Oncol. 2010 January 1; 28(1): 77–82.
Results- Toxicity
Weekly vs Q3W Taxanes
 N= 4950
 AC->Paclitaxel Q3w vs. weekly vs. Docetaxel Q3w vs.
Weekly
 Endpoints
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DFS
OS
 Exploratory Analysis
 Impact of treatment by HER2 status
Soprano, JA et. al. N Engl J Med 2008; 358:1663-1671.
Results
Results
 More neuropathy in the
paclitaxel weekly arm
 Increased Neutropenia
and infection in Docetaxel
Q3w arm
Recurrent or metastatic disease
Recurrent or Metastatic Disease
 Preferred Single Agents
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Doxorubicin
Epirubicin
Paclitaxel
Docetaxel
Capecitabine
Gemcitabine
Vinorelbine
Eribulin
Paclitaxel +Bevacizumab
 Preferred Combinations
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AC
CAF/FAC
FEC
AT
Docetaxel/ Capecitabine
Gemcitabine/ Paclitaxel
Trastuzumab + Other 1st
line agents
Trastuzumab or
Lapatininb+Capecitabine
Trastuzumab + Lapatinib
Combination Anti- HER2 Therapy
 (N = 296)
 Lapatinib + Trastuzumab vs. Lapatinib alone
 PFS ( [HR] = 0.73; 95% CI, 0.57 to 0.93; P = .008)
 CBR (24.7% v 12.4%; P = .01) CR+PR+SD >24 weeks
 OS (HR = 0.75; 95% CI, 0.53 to 1.07; P = .106).
 ORR (10.3% v 6.9; P = .46).
 Most frequent ADR: diarrhea, rash, nausea, and
fatigue; diarrhea was higher in the combination arm
(P = .03).
 Symptomatic cardiac events was low (2% vs 0.7%)
Combination Anti- HER2 Therapy
The Role of Bevacizumab
PFS
Paclitaxel + Bev vs. Paclitaxel
11.8 vs 5.9 mos (P<0.001)
Docetaxel + Bev vs. Docetaxel
10.1 vs. 8.2 mos(P<0.006)
Ribbon-1 Bev Chemo
Capecitabine+ Bev vs Capecitabine
Tax or Anthracycline arm combo
8.6 vs 5.7 mos (P<0.0002)
9.2 vs 8.0 mos (P<0.0001)
•No Increase in OS or QOL when analyzed alone or in meta
analysis
•Modest increase in PFS with the greatest increase seen in
combination with Paclitaxel
•FDA Reversed approval in breast cancer
1Miller,
K. N Engl J Med. 357:2666-2676 (2007). 2 Miles, D. Cancer Res. 69 (Suppl. 3), 495S (2009).
29, 1252–1260 (2011).
3
Robert, N. J. Clin. Oncol.
Eribulin
 Microtubular inhibitor FDA approved in November
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2010 for Metastatic breast cancer after 2 lines of
therapy
Phase III open-label, randomized, multicenter
study(n=762)
2-5 prior CT (≥2 for advanced disease), including an
anthracycline and a taxane, unless contraindicated
Pts were randomized 2:1 to E 1.4 mg/m2 2-5 min IV
bolus on days 1 and 8 of a 21-day cycle or treatment of
physician's choice (TPC)
Endpoint: OS; ORR, PFS, DOR
Eribulin
 Results of Phase III
OS: 13.1 vs 10.6 mos. (HR 0.81, 95% CI 0.66 to
0.99(P=0.041)
 No difference in TTP
 Objective response rate by the RECIST criteria was 11%
(95% CI: 8.6%, 14.3%)
 Median response duration was 4.2 months (95% CI: 3.8,
5.0 months)
 Common ADR: neutropenia, anemia, asthenia/fatigue,
alopecia, peripheral neuropathy (DLT), nausea, and
constipation
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Denosumab
 XGEVA approval to
prevent skeletal-related
events in cancer patients
with solid tumors and
bone metastases
 Human monoclonal
antibody that binds to
RANK ligand, a protein
found on osteoclasts and
involved in bone
breakdown
•Randomized, double-blind,
phase III clinical trial in
women with bone metastases
from breast cancer
•Denosumab 120 mg SQ
monthly vs. Zoledronic acid 4
mg IV monthly
Denosumab Results
•Non-inferiority
Trial
•Delayed the time
to first SRE
•Overall survival
and progressionfree survival were
similar between
arms
Xgeva™ (denosumab)Prescribing information. 2010.Amgen Inc.
Denosumab ADR
 Severe Hypocalcemia
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Corrected serum calcium <7 mg/dL or < 1.75 mmol/L) -3.1%
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Patients with a creatinine clearance less than 30 mL/min or
receiving dialysis are at greater risk of severe hypocalcemia
 Severe Hypophosphatemia
 Serum phosphorus <2 mg/dL or < 0.6 mmol/L -15.7%
 ONJ
 Perform an oral examination and appropriate preventive
dentistry prior to the initiation
 Common ADR fatigue/asthenia, and nausea
NCCN Guidelines Version 2.2011 Invasive Breast Cancer
Denosumab Summary
 Denosumab, Zoledronic acid or pamidronate (all
with Calcium and vitamin D) should be given in
addition to Chemo or endocrine therapy if bone mets
is present, expected survival is > 3 months, and renal
function is adequate
Cervical Cancer
2 ND
3 RD M O S T C O M M O N C A N C E R W O R L D W I D E
78% OF CASES IN DEVELOPING COUNTRIES
MOST FREQUENT CAUSE OF CANCER DEATH IN FEMALES
Cervical Cancer Risk Factors
 Persistent HPV most important contributing factor
 Smoking
 Parity
 Contraceptive use
 Early onset of coitus
 Multiple sexual partner
 History of sexual transmitted disease
 Chronic Immunosuppression
HPV and Cervical Cancer
 Most common sexually transmitted virus in the US
 At least 50% of sexually active people will have HPV
at some point in their lives
 HPV Cause epithelial proliferations at cutaneous and
mucosal surfaces
 20 million Americans 15- 40 years of age (15% of
population)are currently infected
 There are more than 100 types of the virus and about
40 types of HPV are associated with genital HPV
www.cdc.gov/HPV/cancer.html
Human Papillomavirus Types
and Disease Association
mucosal/genital(
~40 types)
high-risk types
16, 18, 31, 45
(and others)
•low grade cervical
abnormalities
•cancer precursors
•anogenital cancers
nonmucosal/cutaneous
(~60 types)
low-risk types
6, 11
(and others)
skin
warts
(hands
and feet)
•low grade cervical
abnormalities
•genital warts
•laryngeal papillomas
http://www.cdc.gov/vaccines/pubs/pinkbook/downloads/Slides/HPV11.ppt
HPV types and disease association
 HPV-16 and HPV-18 are the most prevalent of the
oncogenic types

Associated with cervical, vulvar and vaginal cancers
 HPV- 6 and HPV-11 "low-risk" types can cause
genital warts and usually benign (abnormal but noncancerous) changes in the cervix
 The high efficacy of the vaccines may dramatically
decrease cervical cancer, preventing up to 70% of
newly diagnosed cases
Natural History of HPV Infection
Screening Recommendations
 NCCN adopted the American College of
Obstetricians and Gynecologists screening
recommendations
 Screening should begin at 21 years of age regardless
of sexual intercourse status

Every 2 years between 21 and 29 years of age
 Adolescents who are immunocompromised (HIV,
steroid use, post transplant, etc.) should also have
cervical cytology screened
 Both liquid based and conventional methods of
cervical cytology are acceptable
Screening Recommendations
 Combination of cytology and HPV DNA testing is
appropriate for women greater than 30 years old
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Women who are low risk with both negative result should be
screened every 3 years
HPV DNA testing is not indicated in women < 21 years old
 Women 30 year and older who had 3 consecutive
negative cervical cytology screening test, not
immunocompromised, no history of cervical intraepithelial neoplasia (CIN), not HIV infected, and
were not exposed to DES in utero may extend the
interval between cervical cytology to every 3 years
CDC Vaccines and Immunization
Contact
Information
 Telephone
 Email
 Website
800.CDC.INFO
[email protected]
www.cdc.gov/vaccines
Screening Recommendation
 Women who have been immunized against HPV-16
and HPV-18 should be screened by the same
schedule as non-immunized
 Annual gynecologic examination may still be
appropriate even if cervical cytology is not tested at
each visit
 Women treated in the past for CIN, or cancer
including status post hysterectomy should have
annual screening for at least 20 years after
surveillance
Screening Recommendation
 Screening can be discontinued;
In women who have had a total hysterectomy
for benign indication and have no history of high
grade CIN
 Women between 65 and 70 years of age and older
with 3 or more negative cytology test in a row
and no abnormal test in the past 10 years

HPV DNA Testing
 HPV high risk DNA test- detects whether any of the
14 high risk (oncogenic) types of HPV are present,
does not indicate which type is present
 HPV 16/18- detects whether HPV 16 or 18 is present,
used together with the HPV high-risk DNA test
 Hybrid Capture 2 HPV DNA test- asses whether
women are positive for any of 13 high-risk, falsepositive results due to cross reactivity with nononcogenic subtypes
HPV Vaccines
 Quadrivalent HPV vaccine protect against certain
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types of HPV (6, 11, 16, 18)
Bivalent vaccine protects against HPV 16 and 18
Vaccine most effective if started before intercourse
FDA approved for 9- 26 and 10 – 25 year old females
respectively to prevent cervical cancer and
precancerous lesions due to HPV
Not clear how long immunity is present after
vaccination, data suggest 5- 10 years
Diagnosis of Cervical cancer
 Diagnosis often from cervical cytology, PAP smears
and biopsies (Conization used to determine
invasiveness)
 Colposcopy, and colposcopy directed biopsies is the
primary method for evaluating abnormal cervical
cytology
 CT scans, MRI, PET-CT and surgical staging are used
to guide treatment
Cervical Cancer Staging
Cervical Cancer Treatment
 Surgery for lower stage disease
 Observation is appropriate for lower stage (IA2, IB1, IIA1) and
no risk factors and negative nodes
 Adjuvant XRT indicated if large primary tumor, LVSI,
deep stromal invasion, +LN, +Sx Margins, and +
parametrium
 Chemo-radiation for higher stages or patients who are
not candidates for hysterectomy
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Cisplatin based chemotherapy
Chemo/XRT have shown a 30-50% decrease in risk of death
compared to XRT alone
3 trials have shown improved PFS and OS with Chemo/XRT
Treatment Continued
 Metastatic Disease
 Surgical resection +/- IORT
 Radiation +/- Chemo
 Chemotherapy (Cisplatin Based)
GOG 169
 N= 264
 Cisplatin+ Paclitaxel vs Cisplatin alone
 RR= 36% vs 19%
 PFS= 4.8 mos vs 2.8 os (P= 0.001)
GOG 179
 n= 294
 Randomized Phase III trial
 Cisplatin + Topotecan vs Cisplatin
 RR 27% vs 13% (P=0.004)
 PFS 4.6 mos vs 2.9 mos (P=0.014)
 Median survival 9.4 mos vs 6.5 mos (P= 0.017)
 Increase marrow suppression but no decrease in
QOL
 First study to show survival advantage over single
agent cisplatin
GOG 204
 N= 513 Women with advanced (stage IVB),
recurrent, or persistent cervical cancer
 Cis/ Topotecan, Cis/ Gemcitabine, Cis/Vinorelbine,
vs Cis/ Paclitaxel
 Survival was the primary end point with a 33%
improvement relative to PC considered important
 Closed early due to non-superiority of other
regimens
Monk BJ et al. Phase III Trial of Four Cisplatin-Containing Doublet Combinations in Stage IVB, Recurrent, or Persistent Cervical Carcinoma: A Gynecologic
Oncology Group Study. J Clin Oncol 2009; 27:4649-4655.
GOG 204 Results
Monk BJ et al. J Clin Oncol 2009; 27:4649-4655.
GOG 204
Advantage seen in
women of Hispanic
origin and in
recurrent disease
PFI of 30+ months
Monk BJ et al. J Clin Oncol 2009; 27:4649-4655.
Cervical Cancer Surveillance
 Based on NCCN consensus
 Cervical cytology Q3- 6 mos x 2 years, then Q6 mos
for 3- 5 years, then annually
 Careful surveillance due to increased risk for
secondary cancers at and near radiated sites
Role of a pharmacist
 Drug Interaction screening
 Complementary and Alternative Medications can be prevalent
in cancer patients
 Supportive Care
 Pain Management
 Anti-coagulation Monitoring
 Side Effect Management
 Compliance and Adherence Monitoring
 Increased use of oral chemotherapy medications
 Endocrine therapies
The role of a pharmacist
 Patient education on where to get additional
information
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American Cancer Society www.cancer.org
National Cancer Institute www.cancer.gov
National Comprehensive Cancer Network www.nccn.com
Center for Disease Control and Prevention www.cdc.gov
 Patient Assistance Programs
 NeedyMeds www.needymeds.com
 RxAssist www.rxassist.org
 Prior Authorizations or recommending therapeutic
substitutions to maximize benefits
Question 1
 1. The only cancer for which the Pap test screens is
cervical cancer.
A. True
B. False
Question 2
2. Which of the following recommendation(s) is NOT
true?
A. The USPSTF strongly recommends screening for cervical cancer in
women who have been sexually active and have a cervix.
B. The USPSTF recommends routine screening women older than age
65 for cervical cancer even if they have had adequate recent screening
with normal Pap smears and are not otherwise at high risk for cervical
cancer
C. The USPSTF recommends against routine Pap smear screening in
women who have had a total hysterectomy for benign disease.
D. The USPSTF concludes that the evidence is insufficient to
recommend for or against the routine use of human papillomavirus
(HPV) testing as a primary screening test for cervical cancer.
E. All of the above are true
Question 3
 Which of the following are part of the predictive and
prognostic factors for breast cancer?
A. Hormone receptor status
B. Her2/neu status
C. Axillary node status
D. Tumor Histology
E. All of the above
Question 4
4. The NSABP Breast Cancer Prevention trial showed
a 75% reduction in the occurrence of invasive breast
cancer in patients with atypical ductal hyperplasia
treated with Tamoxifen.
A. True
B. False
Question 5
5. Genetic counseling is recommended for women with
moderate or increased risk of hereditary breast
cancer.
A. True
B False