Breast cancer - part 2

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