Adjuvant hormone therapy

Adjuvant endocrine therapy, in the form of oral antiestrogens-tamoxifen and aromatase inhibitors, alone or in combination with ovarian function suppression for many younger women, reduces the risk of recurrence in early stage breast cancer.

 

 

The decision to use adjuvant endocrine therapy alone, or both adjuvant chemotherapy and endocrine therapy, is guided by a combination of clinical and genomic risk or just clinical risk including standard high-quality pathology measures.

 

Adjuvant endocrine therapy for 5-10 years is recommended for nearly all patients with ER positive breast cancer to prevent metastatic disease, local-original recurrence, and contralateral tumors.

 

Endocrine therapy is effective for a luminal A and lumen B tumor types.

Adjuvant tamoxifen reduces both distant and local regional recurrence by 10-30% when ER expression is moderate and by 40-50% will ER expression is high, with effects lasting 15 or more years.

Adjuvant  endocrine therapy even in subcentimeter, node negative tumors improves outcomes.

Adjuvant tamoxifen reduces the annual rates of breast cancer recurrence by almost half

and mortality by one third.

Adjuvant Tamoxifen in absolute terms translates to 11.8 fewer recurrences and 9.2 fewer deaths per 100 women at 15 years, the benefits being similar for both younger and older women.

The replacement of tamoxifen with aromatase inhibitors results in a 2.7% reduction in the rate of reoccurrence at five years.

The sequential use of aromatase inhibitors after tamoxifen results in an absolute reduction of 2 1/2 percentage points in the rate of recurrence.

No mortality benefit has been shown for the use of aromatase inhibitor’s over tamoxifen.

In postmenopausal women with hormone receptor positive breast cancer who had receive five years of adjuvant endocrine therapy with aromatase inhibitors, extending hormone therapy by five years provided no benefit over a two-year extension but was associated with a greater risk of bone fracture.

Following adjuvant oophorectomy and tamoxifen versus no therapy in premenopausal women with early breast cancer not selected for ER status associated with improved 5 and 10 year disease free survival and overall survival (Love RR).

Ovarian Suppression of Ovarian Function Trial (SOFT):compared adjuvant tamoxifen plus ovarian suppression with tamoxifen alone after median follow up of 67 months.

In the above study 3066 premenopausal women were stratified to received chemotherapy, or no chemotherapy, or to receive 5 years of tamoxifen, tamoxifen plus ovarian suppression, or exemestane plus ovarian suppression.

In the above study after median follow-up of 67 months the estimated disease-free survival at five years was 86.6% in the tamoxifen-ovarian suppression group and 84.7% of tamoxifen alone group.

Adding ovarian suppression to tamoxifen did not provide a significant benefit in overall study population, however in women who were at sufficient risk to receive adjuvant chemotherapy and who remain premenopausal, the addition of ovarian suppression improved disease outcomes.

Improvement was seen with use of Exemesane plus ovarian suppression.

Ovarian suppression of estrogen production reduces the recurrence rate in hormone receptor positive early breast cancer patients who are pre-menopausal.

In premenopausal women randomized to receive chemotherapy or non-chemotherapy and five years of tamoxifen or tamoxifen plus ovarian suppression or aromatase inhibitor plus ovarian suppression: heading ovarian suppression to tamoxifen does not provide a significant benefit and women who receive chemotherapy and who remain premenopausal the addition ovarian suppression improved disease outcome (SOFT Investigators).

Women with early stage hormone receptor positive breast cancer that stay on hormonal therapy for 10 years after initial treatment reduces the risk of recurrence by more than one third, while experiencing no new side effects worsening of quality of life, but did not increase overall survival(Goss P MA.17R trial).

Tamoxifen administered for 10 years continuously or for five years followed by ABCSG-16 phase 3 trial found that postmenopausal women with hormone receptor-positive breast cancer who underwent 5 additional years of anastrozole therapy received no extra benefit compared with women who had 2 years of additional therapy.

an aromatase inhibitor increases disease-free survival by a rate of 2.5-3.5 percentage points, as compared with tamoxifen alone.

In a 10 year follow-up phase III TEAM trial exemestane alone and sequential tamoxifen/exemestane provide similar outcomes as adjuvant endocrine therapy in postmenopausal women with hormone receptor positive early breast cancer (Derks MGM): disease free survival at 10 yesrs was 675 for both groups, 10 year survival was 74 vs 73%, and breast cancer recurrence was 20 vs. 22%.

TailoRx trial demonstrated about 70% of patients with hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative, axillary node-negative early-stage breast cancer, who received intermediate score on the Oncotype Dx test, could be

spared chemotherapy.

The trial found no difference in the disease-free survival whether these women were treated with endocrine therapy alone or with the combination of endocrine therapy with chemotherapy.

The trial found about half of all breast cancers are hormone receptor positive, HER2 negative, and axillary node negative but up to 30% of patients have recurrences by 10 years,

Early Breast CancerTrialists Collaborative Group found a 20 year risk of distant recurrence after five years of endocrine therapy for women with node negative disease, ER positive, early breast cancer is likely about 1/4 lower than previously reported: The risks of distant recurrence during 5-20 years are reported to be 13% for stage T1N0 disease and 19% for those which stage T2N0 disease.

This population can be spared an estimated 70% of patients and limit chemotherapy to the 30% who may benefit from it.

Adjuvant chemotherapy in the above patients reduced the risk for relapse, but the absolute benefit was only 3% to 5%,suggesting many women are being overtreated, because endocrine therapy would be adequate.

ATLAS trial supported the use of 10 rather than five years of adjuvant treatment with tamoxifen: 10 years of tamoxifen reduced the risk for recurrence by 3.7% and the risk for breast cancer mortality by 2.8%

Virtually all studies that compared aromatase inhibitor-based therapy with tamoxifen has demonstrated small disease free survival benefits to those receiving aromatase inhibitors.

The incorporation of aromatase inhibitors as part of adjuvant endocrine therapy is recommended for postmenopausal women, and pre-menopausal women with high risk, hormone receptor positive tumors are considered for ovarian suppression within aromatase inhibitor.

The addition of selective inhibitors of cyclin dependent kinases four and six (CDK4/6 added to hormone therapy in hormone receptor positive HER2 negative patients as adjuvant therapy (MonarchE) abemaciclib improved invasive disease free survival.