This document provides information on treatment for various stages of breast cancer: - Stage III involves locally advanced breast cancer and initial treatment involves neoadjuvant chemotherapy followed by mastectomy, with adjuvant taxane and radiation therapy. - Stage IV involves metastatic breast cancer which is incurable, so treatment goals are disease control, prolonged survival, and palliative care. Therapy choices depend on tumor characteristics and site of metastases, and may include endocrine therapy, chemotherapy, targeted therapy, bisphosphonates, and radiation therapy. - Prognostic factors that influence survival rates include tumor size and characteristics, lymph node involvement, and presence of metastases at diagnosis. Five-year survival rates decrease from 98% for localized cancer to 24

1. Stage III (Locally Advanced Breast CA)
 Many are diagnosed in patients who:
1. Have had symptoms for months to years and have
neglected to seek medical attention.
2. Inflammatory breast Ca (IBCA)
 Neo-adjunctive chemo. should be initial choice of
treatment

2. Locally Advanced Breast CA treatment
Neo-adjunctive AC
chemotherapy
Mastectomy
Adjunctive
Taxane
+/- anti HER2
+/
Radiation to
chest wall
+/-HR
therapy

3. Neo-adjuvant chemotherapy:
 Same chemotherapy as adjuvant therapy. (4 cycles) (>50%
decrease of tumour size, respectable)
Anthracycline-taxane regimen is preferred
Neo-adjunctive hormonal therapy maybe option for Pt. with
unresectable +ve HR tumour who are not able to receive
chemotherapy
Mastectomy/ BCT (?)
Add adjunctive Taxane therapy since it is +ve LN
HER2 (+), use trastuzumab with chemotherapy
Adjunctive radiotherapy should be administered to all stage III
CA to minimize local recurrences.

4. Breast CA Survival Rates
5-year relative survival:
 Localized breast cancer: 98%
 Regional Involvement: 84%
 Distant Involvement: 24%
 Prognostic factors
Tumour size
-ve/+ve LNs
Number of LN
ER/PR
HER2
Note:
Treatment goal of stage I,
II,III, is cure
Age (<35)
Menopausal status
IBC
Gender
Advanced disease at
diagnosis

5. CASE 3
C.D. (37 year-old woman) had a core biopsy performed which revealed
invasive ductal carcinoma. Other staging tests included a CT scan of the
chest, abdomen, and pelvis and a bone scan. All tests were negative.
Physical examination revealed ipsilateral L.N involvement. Mammogram
revealed a 2.2-cm mass in the left breast. She had 2 of 15 LNs positive
for disease
 what stage is C.D.’s breast cancer?
C.D. was diagnosed with stage II, ER +ve & PR+ve, HER2 -ve, invasive
ductal carcinoma of the left breast. Her staging workup was negative as
indicated previously with a negative CT scan of the chest, abdomen, and
pelvis and a negative bone scan.
 Based on this information what would be C.D.’s treatment course/adjunctive
therapy?

6.  Stage IV (metastasis) MBC
Incurable
 Goals:
Rregression of disease (control the disease)
 Prolong survival & improve QoL.
Eventually, shift to supportive /palliative care.
Therapy choice depends on:
Tumour characteristics
 Site of diseases involvement.
Optimizing benefits and minimizing toxicity are general
therapeutic goals of any therapy administered in this setting

7. Endocrine therapy treatment of choice for patients with HR (+)
tumors who exhibit the first sign of metastatic in bone, or pleura.
Pts. with symptomatic visceral (liver) or CNS involvement, SOB,
(more rapidly growing CA) require chemotherapy.
HR (+) & HER2 (+), requiring endocrine therapy in combination
with anti-HER2 therapy
 Pts. (HR+) are sequentially treated with endocrine therapy until
their tumors cease to respond.
Continue HR therapy until disease progression  then switch
agents (but rate & duration of response is lower)

8. Tumors stop to respond HR therapy then chemotherapy can be
administered.
Eventually hormonal therapy will fail
If HR (+), rapidly progressive or symptomatic lung, liver, BM
involvement, progressive disease while on HR therapy, should
treated with chemotherapy.
Aromastase Inhibitors (postmenopausal)
Tamoxifen ‘SERMs’(DOC pre-menopausal).
Cancer recurs at same time or within 1 year of occurrence of
adjuvant tamoxifen, change to other agents (Tamoxifen not DOC)
If an LHRH agonist is used as first-line therapy for MBC, it should
be used in combination with Tamoxifen.

9.  Chemotherapy
Mean survival period after diagnosis MBC 2-4 years.
Single/ sequential chemotherapy is often chosen over
combination.
It is eventually required in most patients with MBC
Ist choice for ER/PR (-)
Choice for HR (+) fail to respond to HR therapy or initially
respond then stop to respond.
Chemo. continued until there is evidence of progressive disease or
intolerable side effects.
Partial response is very common (<10% complete response)

10. Pts. required rapid response to chemotherapy often receive
combination (those with symptomatic bulky metastases).
Combination chemotherapy results response in about 60% of
patients previously unexposed to chemotherapy
Some selected chemotherapy agents used in metastatic stage:
I. Mainly anthracycline /Taxenes.
II. Other agents :
 Flurorouracil
 Capecitabine
 cyclophosphamide
 methotrexate
gemcitabine

11. Anthracyclines and Taxanes are most active classes of
chemotherapy in MBC
If metastases are found within 6 to 12 months of completing
adjunctive therapy with these agents, choose treatment from a
different chemotherapy class.
 Capecitabine (Xeloda)® is first line of treatment for MBC
after failure of Anthracyclines and Taxanes
Capecitabine: 2000–2500 mg/m2/ day orally, divided twice
daily for 14 days. Repeat cycles every 21 days
 Gemcitabine (Gemzar)® 1400mg/m2 IV (30 min) day 1, 8, 15.
(Every 28 days, 4 cycles)

12. Vinorelbine
Palliative therapy
Suitable to pts. Previously treated with Anthracycline and /or
Taxanes (or not suitable to Anth./Tanaxes)
25-30mg/m2 IV for 10 minutes day 1 and 8
4 wks cycle for 6 cycle
S.E: peripheral neuropathy, constipation, myelosuppression
 Vinorelbine + Trsstazumab
Vinorelbine + Capecitabine
Vinorelbine25mg/m2 IV day 1 and 8
Capecitabine 1000mg/m2 bid day 1-14
Every 21 day

13. Paclitaxel + Gemcitabine
Paclitaxel + Bevacizumab
Docetaxel + Capecitabine
Docetaxel 75 mg/m2 IV over 1 hour, day 1
Capecitabine 2,000–2,500 mg/m2 per day orally divided twice daily for 14
days
(Repeat cycles every 21 days)
 Factors associated with an increased response to chemotherapy:
A good performance status
Limited number (one to two) of disease sites or organs.
Long disease-free interval.

14. Biological therapy:
HER2, important protein for maintenance of breast cancer
cell proliferation and survival.
Has significant clinical activity as a single agent
Has synergistic, activity with other chemotherapy agents
Single-agent treatment with trastuzumab yields clinical
benefit rate of nearly 40% in patients with HER2-
overexpressing MBCs
 Supportive therapy
Co-administer bone-modifying agent (Zoledronic acid) to all
breast CA with bone metastases.
Bisphosphonate (Decrease breakdown of bone/ osteoclast).

15.  Decrease rates of skeletal-related events: fractures, spinal
cord compression, pain, need radiation to bones, surgery
4mg IV for 15 minutes
Renal dose
adjustment
(CrCL<60ml/min)
S.E:
Osteonecrosis
in jaw (uncommon)

16. Radiation therapy
Important modality in treatment of symptomatic MBC.
Painful bone metastases or other localized sites of disease
refractory to systemic therapy (pain relief to about 90%)
 Palliative treatment of metastatic brain lesions and spinal
cord lesions, which respond poorly to systemic therapy

17. Case 4:
T.R. is a 65-year-old, postmenopausal woman diagnosed with breast CA
at the age of 48 years. At the time of diagnosis she was premenopausal.
She underwent surgery with a modified radical mastectomy and was
found to have a 1.5-cm invasive ductal carcinoma of the right breast.
She had 2 of 10 L.N +ve. Her breast CA was ER +ve, PR +ve, and
HER2 -ve. T.R. went on to complete adjuvant chemotherapy with AC
therapy for 4 cycles followed by weekly paclitaxel for 12 weeks.
After completion of her chemotherapy, she received 5 years of
tamoxifen therapy.
10 years after completing her therapy, she experiences pain in her right
arm and rib cage. A bone scan revealed metastatic breast cancer.
What would be an appropriate treatment regimen for T.R. at this time?
What other supportive care medicines should be added to T.R.’s
regimen?

18. Continue case 4
T.R. has a long progression free survival on HR therapy. Over the
course of 4 years, she progresses on sequential anastrozole, then
fulvestrant, then exemestane, and then finally megestrol acetate.
Each time she has progressed, the progression free interval has
shortened.
Follow-up staging tests reveal new liver lesions measuring 1 cm
× 1 cm and 2 cm × 1 cm. A CT scan of the chest was -ve. She is
not currently experiencing any symptoms of her disease.
What should the treatment course include now that T.R. is
progressing on hormonal therapy?.

19. THANKS