Locally Advanced Breast Cancer

Special points related to locally advanced breast cancer here
See breast cancer notes for rest.

MANAGEMENT

1. Neoadjuvant Therapy
Has revolutionized the management of locally advanced breast cancer.
Now standard of care for pts with bulky breast or axillary disease.
(And also an option for operable tumours if shrinkage expected to improve eligibility for breast-conserving therapy.

Concerns
- ?increased rates of pre-op complications
- ?alteration of prognostic significance of nodal status.
- ?reduced accuracy of SNL
- ?bad to delay time to surgery.

Now known that there are no adverse effects on surgical complications or survival.
And accuracy of SNL is comparable to those pts undergoing primary surgery
- but need to consider timing:

Neoadjuvant therapy increases the number of women wligible for breast conserving therapy
But no difference in overall survival with neoadjuvant vs adjuvant therapy.
- but pts with a strong ('pathologially complete') response (PCR) to neoadjuvant therapy have a better prognosis.
--> PCR is a surragate endpoint for overall survival.

2. SNL Timing
After neo:
- advantages = proven ok, surgical sequence good;
- disadvantages = FN rates undefined, drug-induced lymph drainage may affect SLN
Before neo:
- advantages: nodal status significance clearer; prognosis up front may help inform treatment decisions
- disadvantages: potentially for unnecessary ALND (chemo sterilizes up to 25-35% of +ve nodes); additional treatment risks.

3. Neoadjuvant Endocrine Therapy?
PCR rate lower than with chemo
But hormone positive patients have a lower response to chemo than hormone negative patients
- so strongly positive ER patients will probably benefit from neoadjuvant endocrine therapy.
Research focus currently on type of endocrine therapy and patient selection.

4. Adjuvant Chemotherapy
Optimal management of patients with residual disease after neoadjuvant therapy is uncertain.
- as for those with do not respond well to initial chemo.
In women with HER2 +ve disease, Trastuzumab is highly effective at improving PCR --> up to 60% (vs 25% without)

Individualized treatment
Pt care must be individualized.
Adjuvant! Online offers a personalized risk tool.
Gene profiling (Oncotype Dx, AMsterdam 70-gene profile) also informative.
- patients with low risk scores can be spared the risk and inconvenience of chemotherapy
- in favour of more effective endocrine therapy.
- high scores = chemo indicated.