1. Introduction to the Management of Breast Cancer

2. Statistics
192,370 new cases and 40,170 deaths estimated for 2009 in the US
62,280 cases in situ breast cancer
Lifetime risk of developing breast cancer is 12-13%, or ~1 in 8 women
Highest incidence
Lifetime risk of dying is approximately 3.0% (1 in 33 women)
Second cancer mortality (after lung ca)
CA Cancer J Clin 2009; 59:

3. Ten Leading Cancer Types for Estimated New Cancer Cases and Deaths, by Sex, United States, 2009
From Jemal, A. et al.
CA Cancer J Clin 2009;59:
Copyright ©2009 American Cancer Society

4. Incidence decreasing 1999-2005, -2.2%
Annual Age-adjusted Cancer Incidence Rates among Males and Females for Selected Cancers, United States,
Incidence decreasing , -2.2%
Death rates decreasing
Absolute change of -8.7%
From Jemal, A. et al.
CA Cancer J Clin 2009;59:
Copyright ©2009 American Cancer Society

5. Incidence and Mortality
Increased screening (mammography)
Environmental factors?
2003 7% decline in incidence (> in ER+)
Decrease in use of hormone replacement therapy
Mortality decreasing
2.3 percent per year from 1990 to 2002
Early detection
Better adjuvant therapy
Ravdin, SABCS 2006
Berry et al NEJM :1784

6. Breast Cancer Risk Factors
Age
Prior breast biopsies with proliferative breast disease
Atypical hyperplasia
Lobular carcinoma in-situ
Family History
Thoracic radiation
Endogenous hormones
Early menarche
Late menopause
Nulliparity or older age at birth of first child
Exogenous hormones
Mammographic density
Lifestyle Factors (alcohol, obesity, diet, exercise)
Intervention – modifiable risk factors … connection is through estrogen

7. Most Breast Cancer is NOT Hereditary
ASCO Curriculum: Cancer Genetics & Cancer Predisposition Testing
Most Breast Cancer is NOT Hereditary
15%-20%
5%–10%
~10%
Breast Cancer
Ovarian Cancer
Sporadic
Family clusters
Hereditary
Breast and Ovarian Cancer 3

8. Comparing Breast Cancer Risk Estimates in BRCA Mutation Carriers
ASCO Curriculum: Cancer Genetics & Cancer Predisposition Testing
Comparing Breast Cancer Risk Estimates in BRCA Mutation Carriers
2% of AJ have BRCA1/2 mutation
BCLC breast cancer linkage consortium
Shows range of reported estimates for BRCA carriers
BRCA1+ carriers
(BCLC)
Breast cancer risk (%)
BRCA1+ carriers
(Ashkenazi Jews)
General population
Age
Easton DF et al. Am J Hum Genet 56:265, 1995
Struewing JP et al. N Engl J Med 336:1401, 1997
Breast and Ovarian Cancer 7

9. ACS Screening Recommendations
Test or Procedure
Frequency
Breast
Breast self-examination
Monthly, starting at age 20
Clinical breast examination
Every 3 years from ages
Annually, starting at age 40{a}
Mammography
Annually, starting at age 40
20% of breast cancers not seen on mammo
When do you stop screening mammography?

10. ACS guidelines for Breast MRI
CA Cancer J Clin 2007; 57; 75-89

11. Diagnosis of Breast Cancer
Fine needle aspiration
Cytologic diagnosis, cannot distinguish DCIS from invasive disease
Negative aspiration does not rule out cancer
Core-needle biopsy
Preferred method for diagnosis; preserves architecture
Excisional biopsy
Useful to determine tumor size
Precludes primary chemotherapy
Needle localization
Nonpalpable lesions, multiple lesions
Stereotactic biopsy
Image-guided FNA or core biopsy

12. Breast Cancer Pathology
Invasive carcinoma
Infiltrating ductal (75% of breast cancers)
Infiltrating lobular (5-10% of breast cancers)
“Indian file” histology, less distinct mass
More often metastasizes to: pleura, peritoneum, meninges
Medullary (5-7%)
Lymphocytic and plasma cell infiltrate, well circumscribed
Good prognosis
Mucinous/Colloid (3%,)
Papillary (1-2%)
Tubular (5 %)

13. Breast Cancer Pathology
Non-invasive tumors
Ductal carcinoma in situ (DCIS)
Comedo (poorly differentiated)
Noncomedo (well differentiated, low-grade)
Papillary, micropapillary, cribiform, solid
Lobular carcinoma in situ (LCIS)
Uncommon tumors
Inflammatory carcinoma
Paget’s disease
Phyllodes tumor (cystosarcoma phyllodes)

14. Breast Cancer Classification
Staging (TNM)
Histologic evaluation
Tumor grade
Hormone receptors
HER2 expression
Molecular subtypes

15. Prognostic Factors Patient age (menopausal status) Tumor size
# of Lymph nodes
Histologic tumor type
Tumor grade (% tubule formation, nuclear pleomorphism, mitotic count)
Hormone receptor status
Her2/neu status
Oncotype DX score/ Recurrence score

16. Natural History
Fig 1. (A) Relapse free survival (RFS) based on size for entire cohort 1 (0.1 to 1.0 cm, top); entire cohort 2 (1.1 to 2.0 cm, middle); and entire cohort 3 (2.1 to 5.0 cm, bottom)
82%
75%
66%
N=1187. No adjuvant chemo/hormones therapy. To determine natural history. Show effect of tumor size and ER status
Excluded LN + and LVI+
54%ER +
Chia, S. K. et al. J Clin Oncol; 22:

17. Risks of Mortality by Tumor Type in Women aged 50-79 yrs
SEER (164,958 pts)
Histology
Ductal
Lobular
Mucinous
Medullary
Tubular
Papillary
Survival (%)
58.7 67
65.3
55.2
81.5
62.8
HR 995% CI)
1.00 (reference)
0.89 ( )
0.80 ( )
0.82 ( )
0.66 ( )
0.81 ( )
Adjusted for age at diagnosis, year of diagnosis, SEER historic stage, registry, surgical treatment and radiation therapy
No data on chemo or hormonal use available
Li, et al Arch Int Med 163: , 2003

18. Tumor Grading
Tumor grade is a system used to classify cancer cells in terms of how abnormal they look under a microscope and how quickly the tumor is likely to grow and spread

19. Hormone receptor status
Estrogen and progesterone receptors are nuclear transcription factors
Determined by immunohistochemistry
Scored as a percentage of cells staining
1% or greater is considered positive

20. Her2/neu status
Membrane-associated tyrosine kinase receptor (aka erbB2)
Expressed in breast cancers, DCIS, and some other tissues such as heart
Worse prognosis with HER2 gene amplification
Prognosis changing with use of trastuzumab

21. Her2/neu status Measured by immunohistochemistry (IHC) and/or FISH
FISH more accurate
IHC: Graded 0, 1+, 2+, or 3+
Based on characteristics of staining
0-1 = negative
2 = in determinant, should be followed with FISH (fluorescent in situ hybridization) to determine status (amplified/not amplified)
3 = positive

22. Prognosis: Tumors  1 cm, HER2 gene amplification, Node-negative
Press, M et al. J Clin Oncol 15: , 1997

23. The HER Family of Receptors
Lapatinib
HER3
HER1
EGFR
HER2
HER4
Tumor Cell
The human epidermal growth factor family of receptors consists of 4 transmembrane proteins with different properties (HER1-4), all involved in regulation of cell proliferation and survival.1-5
The prototype HER member HER1/EGFR (Erb-B1) binds a variety of growth factors, with ligand binding activating tyrosine kinase activity within the cytoplasmic domain and through various signal transduction intermediates.1
HER2 has no known ligand-binding activity, but its tyrosine-kinase activity is transactivated through HER2 interaction with other HER members (heterodimerization), usually following ligand binding to those receptors.3
The HER2 extracellular domains are fixed in an open conformation (exposed domain II loop) that resembles a ligand-activated state, and thus HER2 can constitutively interact functionally with other HER members.6
HER3 lacks inherent tyrosine kinase activity, but ligand binding promotes HER heterodimerization, resulting in complexes (eg, HER2/HER3) with highly proliferative signaling activity.2,4
The HER signaling network, mediated by these receptor interactions, stimulates and regulates not only cell proliferation, but also mobility, adhesion and survival.4,5 The activity of HER2/HER4 dimers is unclear, but may be implicated in providing survival signals to cardiomyocytes.4,5
Trastuzumab (Herceptin)
Pertuzumab (Omnitarg)
1. Ritter and Arteaga. Semin Oncol. 2003;30(suppl 1):3.
2. Hung and Lau. Semin Oncol. 1999;26(suppl 12):51.
3. Tzahar and Yarden. Biochim Biophys Acta. 1998;1377:M25.
4. Pinkas-Kramarski et al. EMBO J. 1996;15:2452.
5. Zhao et al. J Biol Chem. 1998;273:10261.
6. Cho et al. Nature. 2003;421:756.

24. Her2 therapy Trastuzumab (Herceptin) Lapatinib (Tykerb)
Monoclonal antibody directed towards Her2/neu receptor
cardotoxicty
Lapatinib (Tykerb)
Small molecule tyrosine kinase inhibitor blocking HER2 and EGFR1 (HER1)
Diarrhea, rash
Cardiotoxicity?

25. Molecular Portrait of Breast Cancers
“Normal”
Luminal B
HER-2
Basal-like
Luminal A
This is seminal working from Torres Sorlie, Chuck Perou, and the Brown bostein lab to look at molecular profiles in breast cancer. In this figure, genes that are upregulated are expressed in red, those down regulated are expressed as green. When Sorlie and Perou performed statistical analysis on the gene expression profiles of breast cancers, they found that the cancers segregated into 5 clusters. Two luminal clusters, luminal A and B, that most closely resembled luminal epithelium. A Normal group who’s profile most closely resembled normal breast tissue, the basal like group I’ll discuss here, and the her-2 group, which had previously been identified immunohistochemically…
Sorlie T et al, PNAS 2001
Slide courtesy of L. Carey

26. Proxies for Gene Signature “Subtypes”
Triple Negative
ER/PR+
HER2+ ER/PR-
Basal-like
75% 9% 0%
Luminal
12%
76%
14%
“HER2” 5%
85%
Unfortunately, it is not yet practical to perform gene expression profiling on all tumors; however, we have reasonable “proixes” for the relevant subtypes; the worst, “basal-like” is associated with ER-/PR-/Her-2 negative cancers. “luminal” are predominantly ER/PR+, and the Her-2 subtype is Her-2 positive.
Note that these are prognostic… and so are modifiable by therapy.
Courtesy of L Carey

27. Subtypes and Prognosis
It turns out that these clusters described cancers with different prognoses. We are paying special attention now to the basal-like subtype in red because of this poor prognosis
Sorlie T et al, PNAS 2001

28. 2003 AJCC: Primary Tumor (T)
T1:  2 cm
T1mic microinvasion  0.1 cm
T1a > cm
T1b 0.6 – 1 cm
T1c 1.1 – 2 cm
T2: cm
T3: > 5 cm
T4a: Extension to chest wall, not including pectoralis
T4b: Edema, ulceration, satellite skin nodules
T4c: both T4a and T4b
T4d: inflammatory ca

29. AJCC 2003: Stage Grouping Stage 0 Tis N0 M0 Stage I T1 Stage IIA T0 N1
Stage IIB T3
Stage IIIA
T0-3 N2
Stage IIIB T4
N0-2
Stage IIIC
Any T N3
Stage IV
Any N M1

30. Staging Classification of Breast Tumour

31. Therapy of Breast Cancer
Local:
Surgery
Mastectomy
Breast Conserving Therapy
SLND/ALND
Radiation therapy
Systemic:
Endocrine/hormonal therapy
Chemotherapy
Biologic therapy

32. Breast Cancer Local Treatment
Modified radical mastectomy with axillary lymph node dissection
Breast-conserving therapy – lumpectomy with axillary lymph node dissection followed by radiation
Equivalence established by NSABP B-06
Original report (Fisher, et al., NEJM 1985)
12 year follow up (Fisher, et al., NEJM 1995)
NCI audit (Christian, et al., NEJM 1995)

33. Surgical Treatment for early stage localized breast cancer
Lumpectomy (partial mastectomy/
breast conserving therapy)
Mastectomy
Total (simple)
Subcutaneous
Modified Radical
Radical
Breast reconstruction is a part of treating a woman with a mastectomy
-Lumpectomy- aka. Partial mastectomy, aka. Breast conserving therapy; most common form of breast cancer surgery today. Remove the “tumor” plus margins and give radiation
-total (simple) mastectomy = removal of both breasts and overlaying skin without axillary dissections
-subcutaneous mastectomy = removal of both breasts with preservation of the overlying skin and nipple-areolar complexes
-modified radical mastectomy = removal of both breasts (not the pectoralis muscles) with overlaying skin and axillary contents
-radical mastectomy = removal of both breasts with overlaying skin, pectoralis muscles, and axillary contents. 33

34. Contraindications to BCT
Pregnancy
Previous breast or mantle RT
Diffuse malignant microcalcifications
Collagen vascular disease (SLE, scleroderma)
Multicentric disease

35. Indications for Post-Mastectomy Radiation
4 or more positive axillary lymph nodes
Tumor 5 cm or greater
Tumor invading the skin or adjacent musculature
Positive surgical margins
Note: Role in patients with 1 – 3 positive nodes is controversial (balanced discussion)
ASCO guidelines for postmastectomy XRT
Recht, et al., JCO 19:1539, 2001.

36. Adjuvant systemic therapy
Can eliminate hidden, microscopic metastases
Decreases local recurrence in patients treated with breast conservation
Includes:
Hormone therapy
Chemotherapy
Target therapy (ie Herceptin) 36 36

37. Who should receive adjuvant therapy?
Consensus statements:
Early Breast Cancer Trialists’ Collaborative Group (EBCTCG, aka Oxford Overview) last published 2005
7th International Conference on Adjuvant Therapy of Primary Breast Cancer (St. Gallen, 2009)
NCI Consensus Conference (Nov 2000)
NCCN guidelines
Oxford overview 2005 publication was from the 2000 meeting

38. Indications for Adjuvant Chemotherapy
All lymph node-positive
Her2/neu positive tumors
Triple negative tumors
Invasive, lymph node-negative
- invasive ductal/lobular, > 1 cm (NIH)
- invasive ductal/lobular, > 2 cm (St. Gallen’s)
- invasive, favorable histology, > 3 cm

39. Case#1
68 y.o. postmenopausal female noted to have abnormality in left breast on screening mammogram
approx 1 cm abnormality noted in upper outer quadrant
No sig PMH or FH
Negative ROS

40. Left core biopsy-infiltrating ductal carcinoma, grade 1, ER 90%, PR 95%, Her2/neu negative

41. Left lumpectomy and SLNB-1.1cm IDC, 0/2LN+
What adjuvant therapy should she receive?

42. Hormonal treatment first choice Could consider chemotherapy
Oncotype DX

43. Indications for Adjuvant Hormonal Therapy
Indicated for almost all patients with ER or PR expression > 1%
Sequential preferred over concurrent chemo-hormonal therapy
Tamoxifen and/or AI
No AI in premenopausal women
Need references for sequential/concurrent
Albain, K. St Gallen Conf 2003

44. Hormonal (Endocrine) Therapies: Mechanisms of Action
Decrease ligand
Aromatase inhibitors
Oophorectomy
Goserelin, Leuprolide
Block receptor
SERM (selective estrogen receptor modulators)
SERD (selective estrogen receptor downregulator)

45. Diff hormonal agents Tamoxifen
Blood clots, uterine cancer, increased LFTs, cataracts, hot flashes
Improves BMD in postmenopausal, improves lipid profile
Aromatase Inhibitors (anastrozole, letrozole, exemestane)
Myalgias/arthralgias, decrease in BMD
Elevate BP, elevate lipids, CV risk?

46. Adjuvant Therapy Guiding Principles: Hormones
EBCTCG Lancet. 365(9472):

47. EBCTCG tamoxifen in subgroups
Tamoxifen benefits all groups:
Older and younger
Chemo or not
Lymph node + or not
EBCTCG Lancet :

48. Trials of AIs in the adjuvant setting
TAMOXIFEN x 5
ATAC
ANASTROZOLE x 5
TAM + ANAST x 5
TAMOXIFEN x 5
LETROZOLE x 5
BIG I-98
TAM x 2
LET x 3
LET x 2
TAM x 3
TAM x 2-3
IES
TAM x 2-3
EXEMESTANE x 2-3
ABCSG 8
TAM x 2-3
ARNO 95
TAM x 2-3
ITA
Anastozole x 2-3
LETROZOLE x 5
MA-17
TAMOXIFEN x 5
PLACEBO x 5

49. Summary of Results from Large Adjuvant Aromatase Inhibitor Trials
0.4
0.6
0.8
1.0
1.2
BIG I-98
0.81 (0.70, 0.93)
ABSCG/
ARNO
0.60 (0.44, 0.81)
ATAC
0.83 (0.73, 0.94)
MA.17
0.58 (0.45, 0.76)
IES
0.76 (0.66, 0.88)

50. Length of Hormonal Tx
Atleast 5 years
Up to 10 years
Maybe more?

51. Endocrine Rx: What you need to know
Use in anyone with ER+ and/or PR+
Sequence after chemotherapy
Tamoxifen reduces the risk of recurrence and improves overall survival across the board
AIs reduce risk of recurrence compared with tamoxifen. NO increased OS yet.
Try to use AIs in all postmenopausal women
SERM and AI side effect profiles differ, keep in mind when assessing individual patients
Ovarian suppression is an option for premenopausal women (added benefit with hormonal tx?)

52. Case #2
48 y.o. perimenopausal female notes a 1.5 cm mass in her right breast on self exam
Mammogram shows no abnormalities

53. Biopsy-IDC, grade 3, ER 30%, PR 10%, Her2/neu negative

54. Lumpectomy and SLNB-2cm IDC, grade 3, 1/2 LN+
What should she receive as adjuvant therapy?

55. Lymph Node Positive Breast Cancer
ER negative
chemotherapy
(pre-menopausal or post-menopausal)
ER positive
premenopausal: chemotherapy + tamoxifen**
postmenopausal: tamoxifen/AI +
- age > 70: tamoxifen (+ chemotherapy?)
** ovarian ablation/GnRH analog may be considered

56. Adjuvant!
Computer program to determine breast cancer prognosis by adjuvant therapy
Recurrence rates based on Oxford Overview data
Overall survival based on SEER data

57. Adjuvant Online

58. Adjuvant Online Printout

59. Genomic Health 21 Gene Panel Predicts Benefit from Chemotherapy - Results from NSABP B-14 and B-20
Soonmyung Paik1, Steven Shak2, Gong Tang1, Chungyeul Kim1, Joffre Baker2, Maureen Cronin2, Rick Baehner2, Drew Watson2, John Bryant1, Joseph Costantino1, William Hiller1, and Norman Wolmark1
From
1. Division of Pathology, Operation Center, and Biostatistics Center, NSABP, Pittsburgh, PA
2. Genomic Health, Inc., Redwood City, CA

60. Oncotype DX 21 Gene Recurrence Score (RS) Assay
16 Cancer and 5 Reference Genes From 3 Studies
PROLIFERATION
Ki-67
STK15
Survivin
Cyclin B1
MYBL2
ESTROGEN ER PR
Bcl2
SCUBE2
GSTM1
BAG1
INVASION
Stromolysin 3
Cathepsin L2
CD68
Category
RS (0 – 100)
Low risk
RS < 18
Int risk
RS ≥ 18 and < 31
High risk
RS ≥ 31
REFERENCE
Beta-actin
GAPDH
RPLPO
GUS
TFRC
HER2
GRB7

61. Validation Study of Oncotype DX
Tamoxifen treated patients from NSABP B-14 (N=668)
Performance exceeded standard measures of patient age, tumor size
338 pts
149 pts
181 pts

62. OncotypeDX Results
I would then refer back again to the patient KL, whose Adjuvant! Predictions we saw earlier. She underwent Oncotype Dx testing and, perhaps surprisingly, her risk turne out to be in the “low risk” category. What should be recommended for her? According to Adjuvant, she would expect an 8% absolute risk reduction with chemotherapy. According to Oncotype Dx, with only a 9% rate of distant recurrence, chemotherapy could only benefit her by 3%-4%.

63. Oncotype Dx: Chemotherapy benefit
RS < RS RS ≥ 31
Patients with tumors that have high Recurrence Scores have a large absolute benefit of chemotherapy (similar results with CMF and MF)
Patients with tumors that have low Recurrence Scores derive minimal, if any, benefit from chemotherapy
Paik et al, J Clin Oncol. 2006;Epub May 23.

64. EBCTCG: Chemotherapy reduces risk of recurrence
<50 years
years
The most important information regarding the benefit of chemotherapy comes from the EBCTCG which meet every 5 years to go thru data from global cancer trials. This analysis the benefit of chemotherapy in women who received chemotherapy compared to those that did not. On the left here, you can see the benefit of chemotherapy in women <50 years who did and did not receive chemotherapy. On the right, the benefit of chemotherapy is divided for women between the age of The gains are more marked in premenopausal women. These benefits are twice as great at 15 For women under 50, women randomized to a combination of chemotherapy agents compared with no treatment reduced the risk of disease relapse by 37% and death by 30% and a 15 year that translated into a 10% absolute survival benefit. For women aged 50-69years, the risk of relapse was reduced by 19% and the risk of death 12% which translated into a 3% absolute gain in 15yr survival. Important to remember these are the benefits seen without the addition of taxanes, dose dense scheduling and herceptin based treatment…so could be more
EBCTCG Lancet. 365(9472):

65. Progress in Adjuvant Chemotherapy
of Breast Cancer
1970s
Before Anthracyclines
CMF, CMFVP
With Anthracyclines
Combination: AC, FAC, FEC, CEF
Sequence and Alternating
Dose intensity, dose density, HDCT
Taxanes (Paclitaxel/Docetaxel)
Sequential: A → T → C or AC → T
Combination: TA, TAC
Biologic Modifiers
1980s
The bottom line is that the regimens are getting more sophisticated, using very active drugs and combining with biologic agents with the idea of tailoring the therapy to the patient--- here is an example of that.
1990s
2000s
Vogel CL, ASCO 2003

66. Adjuvant Chemotherapy Regimens
Low risk/lymph node negative
ACx4
CMFx6
CAFx6
TCx4
High risk/lymph node positive
dd ACx4paclitaxel x4 (q2 week)
TACx6
FEC-100 or CAFx6 if taxane not tolerated
TC 4-6 cycles if anthracycline not tolerated
Her2+
Herceptin based regimen

67. Neoadjuvant Therapy Indications Inoperable tumors
Inflammatory breast cancer
May consider to increase chance for BCS
In operable breast cancer where chemotherapy is recommended, neoadjuvant therapy can be considered
No difference in DFS or OS between neoadjuvant and adjuvant Rx
Patients with pCR after neoadjuvant Rx have > 90% OS (reported rates range of pCR 4-65%)
The optimal approach to staging the axilla in patients getting neoadjuvant Rx is not known
This impacts surgery and radiation therapy

68. Surveillance
History and physical every 4-6 months for 5 years, then annually
Mammogram annually (and at 6 months after treatment with XRT and breast conserving surgery)
Pelvic exam annually for women with intact uterus on tamoxifen
Other imaging only as indicated by history and physical exam

69. Case #3
56 y.o. female with newly diagnosed stage III right breast cancer (IDC, gr 2, ER+, PR-, Her2/neu-)
On staging studies found to have multiple bony lesions on bone scan and suspicious liver lesions on CT

70. Liver bx-consistent with metastatic breast cancer
What do you do?

71. Disease Recurrence ER+ ER- Biopsy ER, PR, HER2/neu status ER+
Hormonal
therapy
ER+
ER-
Up to 20% of discordance can exist between the primary and the metastatic lesions in ER/PR status, either as a function of technical assay variability or biologic heterogeneity. Furthermore, tumors can acquire Her-2/neu positivity either due to clonal selection et cetera.
Chemotherapy +
Trastuzumab
Hormonal
Therapy +/- Trastuzumab
Chemotherapy
2nd line/3rd line
hormonal
therapy
Chemotherapy
Chemotherapy +
Trastuzumab

72. Metastatic disease: General principles
Hormonal therapy for indolent disease
Trastuzumab-based therapy for HER2/neu positive disease
Single agent chemotherapy for aggressive/symptomatic disease or disease not responsive to hormonal therapy
Consider tx with bevacizumab
Polyagent chemotherapy for visceral crisis or disease requiring rapid response

73. History of Drug Approvals for Breast Cancer
General approvals
Methotrexate Dec 1953
Cyclophosphamide Nov 1959
Doxorubicin Aug 1974
1st Breast Cancer Approval
Paclitaxel Apr 1994
Docetaxel July 1994
Capecitabine Mar 1998
Pamidronate Sept 1998
Trastuzumab Sept 1998
Epirubicin Sept 1999
Abraxane Jan 2005
Bevacizumab Feb 2008
Hormonal
Tamoxifen Dec 1977
Anastrozole Dec 1995
Goserelin Dec 1995
Toremifene May 1997
Letrozole July 1997
Exemestane Oct 1999
Fulvestrant Apr 2002

74. Metastatic Breast Cancer
Not curable
1st recurrence should be biopsied!!
1st goal is to maintain good QOL – consider it a chronic disease
Bisphosphonates for bone metastases

75. Metastatic disease
Tumor markers not shown to be helpful in making clinical decisions
Restaging studies every 3 to 6 months to determine progression, sooner if symptomatic, clinically warranted
Clinical trials!

76. High Dose Chemotherapy with Stem Cell Rescue
Toxicities are substantial, including a 5-8% mortality in past, 1-2% at present
Overall survival benefit has not been demonstrated; relapse-free benefit is controversial in high risk patients
No proven benefit in metastatic disease
Should be done only on clinical trials

77. Conclusions Many effective treatment regimens
Efforts now focused on defining subtypes to individualize treatment and avoid overtreatment

78. Questions???