This document summarizes several nonsurgical breast cancer therapies, including radiation therapy, chemotherapy (adjuvant and neoadjuvant), hormone therapies like tamoxifen and aromatase inhibitors, ablative endocrine therapy with aminoglutethimide, and anti-HER2 therapies like trastuzumab, lapatinib, and ado-trastuzumab emtansine. It provides details on how and when each therapy is used, potential side effects, and outcomes from clinical trials to establish recommendations for treating different cancer stages and receptor statuses.

1. NONSURGICAL BREAST
CANCER THERAPIES
Ashvini bavda

2. Outline
• Radiation Therapy
• Chemotherapy Adjuvant
• Antiestrogen Therapy
• Ablative Endocrine Therapy
• Anti–HER-2/neu Therapy
Radiation Therapy
Chemotherapy Adjuvant
Antiestrogen Therapy
Ablative Endocrine Therapy
Anti–HER-2/neu Therapy
Outline

3. Radiation Therapy
• Used for all stages of breast cancer
depending on whether the patient is
undergoing BCT or mastectomy

4. Radiation Therapy
• Current recommendations for stages IIIA and IIIB breast
cancer are:
(a) Adjuvant radiation therapy to the breast and
supraclavicular lymph nodes after neoadjuvant
chemotherapy and segmental mastectomy with or
without axillary lymph node dissection

5. Radiation Therapy
(b) Adjuvant radiation therapy to the
chest wall and supraclavicular lymph
nodes after neoadjuvant chemotherapy
and mastectomy with or without axillary
lymph node dissection,

6. Radiation Therapy
(c) Adjuvant radiation therapy to the
chest wall and supraclavicular lymph
nodes after segmental mastectomy or
mastectomy with axillary lymph node
dissection and adjuvant chemotherapy

7. Chemotherapy Adjuvant
• The Early Breast Cancer Trialists’
Collaborative Group overview analysis of
adjuvant chemotherapy demonstrated
reductions in the odds of recurrence and
of death in women ≤70 years of age with
stage I, IIA, or IIB breast cancer.

8. Chemotherapy Adjuvant
• Adjuvant chemotherapy is of minimal
benefit to women with negative nodes and
cancers ≤0.5 cm in size and is not
recommended.

9. Chemotherapy Adjuvant
• Negative nodes and cancers 0.6 to 1.0 cm
are divided into those with a low risk of
recurrence and those with unfavorable
prognostic features that portend a higher
risk of recurrence and a need for adjuvant
chemotherapy

10. Chemotherapy Adjuvant
• Adverse prognostic factors:
• blood vessel or lymph vessel invasion,
• high nuclear grade
• high histologic grade
• HER-2/neu overexpression,
• negative hormone receptor status.

11. Chemotherapy Adjuvant
• Adjuvant chemotherapy is recommended
by the NCCN guidelines for women with
these unfavorable prognostic features

12. Chemotherapy Adjuvant
 Hormone receptor-negative cancers that
are >1 cm in size = adjuvant
chemotherapy
• Special-type cancers (tubular, mucinous,
medullary, etc) are usually strongly
estrogen receptor positive, adjuvant
antiestrogen therapy advised for cancers
>1 cm.

13. Chemotherapy Adjuvant
• Node-positive tumors or with a special-
type cancer that is >3 cm, the use of
chemotherapy is appropriate
• Those with hormone receptor positive=
antiestrogen therapy.

14. Chemotherapy Adjuvant
• Stage IIIA breast cancer preoperative
chemotherapy with an anthracycline-
containing or taxane-containing regimen
followed by either a modified radical
mastectomy or segmental mastectomy
with axillary dissection followed by
adjuvant radiation therapy should be
considered, especially for estrogen
receptor negative disease

15. Neoadjuvant (Preoperative)
Chemotherapy
• The use of neoadjuvant chemotherapy
offers the opportunity to observe the
response of the intact primary tumor and
any regional nodal metastases to a
specific chemotherapy regimen

16. Neoadjuvant (Preoperative)
Chemotherapy
• After treatment with neoadjuvant
chemotherapy, patients are assessed for
clinical and pathologic response to the
regimen.
• Patients whose tumors achieve a
pathologic complete response to
neoadjuvant chemotherapy have been
shown to have statistically improved
survival outcomes.

17. Neoadjuvant (Preoperative)
Chemotherapy
• Patients who experience progression of
disease during neoadjuvant chemotherapy
have the poorest survival

18. Neoadjuvant (Preoperative)
Chemotherapy
• Current NCCN recommendations for
treatment of operable advanced local-
regional breast cancer are neoadjuvant
chemotherapy with an anthracycline-
containing or taxane-containing regimen
or both, followed by mastectomy or
lumpectomy with axillary lymph node
dissection if necessary, followed by
adjuvant radiation therapy.

19. Neoadjuvant (Preoperative)
Chemotherapy
• HER-2-positive breast cancer,
trastuzumab can be combined with
chemotherapy in the preoperative setting
to increase pathologic complete response
rates.

20. Neoadjuvant (Preoperative)
Chemotherapy
• Inoperable stage IIIA and for stage IIIB
breast cancer, neoadjuvant chemotherapy
is used to decrease the local-regional
cancer burden.
• This may then permit subsequent modified
radical or radical mastectomy, which is
followed by adjuvant radiation therapy

21. Nodal Evaluation in Patients
Receiving Neoadjuvant
Chemotherapy
• Standard practice has been to perform an
axillary lymph node dissection after
chemotherapy or to perform a sentinel
lymph node dissection before
chemotherapyfor nodal staging before
chemotherapy is initiated.

22. Neoadjuvant Endocrine
Therapy
• It has most commonly been used in
elderly women who were deemed poor
candidates for surgery or cytotoxic
chemotherapy

23. Neoadjuvant Endocrine
Therapy
• As age increased, women obtained less
benefit from chemotherapy
• ER-positive tumors do not shrink in
response to chemotherapy as readily as
ER-negative tumors

24. Neoadjuvant Endocrine
Therapy
• Neoadjuvant endocrine therapy has been
shown to shrink tumors, enabling breast-
conserving surgery in women with
hormone receptor-positive disease who
otherwise would have to be treated with
mastectomy

25. Neoadjuvant Endocrine
Therapy
• Including tumor estrogen receptor
concentration, nuclear grade, histologic
grade, tumor type, and markers of
proliferation should be considered in these
patients before choosing between the use
of chemotherapy and hormonal therapy

26. Neoadjuvant Endocrine
Therapy
• Adjuvant trials the primary endpoint is
typically survival, whereas in neoadjuvant
trials the endpoints have more often been
clinical or pathologic response rates

27. Antiestrogen Therapy
• Tamoxifen
• Aromatase inhibitors

28. Ablative Endocrine Therapy
• Aminoglutethimide:
• Blocks enzymatic conversion of
cholesterol to γ-5-pregnenolone and
inhibits the conversion of androstenedione
to estrogen in peripheral tissues.

29. Ablative Endocrine Therapy
• Dose-dependent and transient side effects
include ataxia, dizziness,and lethargy
• After treatment with this agent (medical
adrenalectomy), adrenal suppression
necessitates glucocorticoid therapy.
• Neither permanent adrenal insufficiency
nor acute crises have been observed.

30. Ablative Endocrine Therapy
• Because the adrenal glands are the major
site for production of endogenous
estrogens after menopause, treatment
with aminoglutethimide has been
compared prospectively with surgical
adrenalectomy and hypophysectomy in
postmenopausal women and is equally
efficacious

31. Anti–HER-2/neu Therapy
• The determination of tumor HER-2/neu
expression or gene amplification for all
newly diagnosed patients with breast
cancer is now recommended
• It is used to assist in the selection of
adjuvant chemotherapy in both node-
negative and nodepositive patients.

32. Anti–HER-2/neu Therapy
• Patients with HER-2-positive disease
appear to have better outcomes with
anthracycline-based adjuvant
chemotherapy regimens.
• Patients with HER-2-positive tumors
benefit if trastuzumab is added to
paclitaxel chemotherapy.

33. Anti–HER-2/neu Therapy
• Cardiotoxicity may develop if trastuzumab
is delivered concurrently with
anthracycline-based chemotherapy

34. Anti–HER-2/neu Therapy
• Trastuzumab :
was initially approved for the treatment of
HER-2/neu–positive breast cancer in
patients with metastatic disease

35. Anti–HER-2/neu Therapy
Lapatinib:
 Dual tyrosine kinase inhibitor that targets
both HER-2 and EGFR
It was approved for use with capecitabine
in patients with HER-2-positive metastatic
disease

36. Anti–HER-2/neu Therapy
• Ado-trastuzumab:
Approved for patients who have previously
received trastuzumab and a taxane either
separately or in combination.
Binds to the HER-2 receptor and releases
a cytotoxic agent into the cell that leads to
apoptosis

37. Anti–HER-2/neu Therapy
• Pertuzumab:
Targets the HER-2 receptor, in
combination with trastuzumab and
docetaxel for treatment of metastatic HER-
2-positive breast cancer

38. Thank you