Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2018-04-10
Efficacy of Chemotherapy for ER-Negative and ER-Positive Isolated Locoregional Recurrence of Breast Cancer: Final Analysis of the CALOR Trial.
Abstract
Purpose Isolated locoregional recurrence (ILRR) predicts a high risk of developing breast cancer distant metastases and death. The Chemotherapy as Adjuvant for LOcally Recurrent breast cancer (CALOR) trial investigated the effectiveness of chemotherapy (CT) after local therapy for ILRR. A report at 5 years of median follow-up showed significant benefit of CT for estrogen receptor (ER)-negative ILRR, but additional follow-up was required in ER-positive ILRR. Patients and Methods CALOR was an open-label, randomized trial for patients with completely excised ILRR after unilateral breast cancer. Eligible patients were randomly assigned to receive CT or no CT and stratified by prior CT, hormone receptor status, and location of ILRR. Patients with hormone receptor-positive ILRR received adjuvant endocrine therapy. Radiation therapy was mandated for patients with microscopically involved margins, and anti-human epidermal growth factor receptor 2 therapy was optional. End points were disease-free survival (DFS), overall survival, and breast cancer-free interval. Results From August 2003 to January 2010, 162 patients were enrolled: 58 with ER-negative and 104 with ER-positive ILRR. At 9 years of median follow-up, 27 DFS events were observed in the ER-negative group and 40 in the ER-positive group. The hazard ratios (HR) of a DFS event were 0.29 (95% CI, 0.13 to 0.67; 10-year DFS, 70% v 34%, CT v no CT, respectively) in patients with ER-negative ILRR and 1.07 (95% CI, 0.57 to 2.00; 10-year DFS, 50% v 59%, respectively) in patients with ER-positive ILRR ( Pinteraction = .013). HRs were 0.29 (95% CI, 0.13 to 0.67) and 0.94 (95% CI, 0.47 to 1.85), respectively, for breast cancer-free interval ( Pinteraction = .034) and 0.48 (95% CI, 0.19 to 1.20) and 0.70 (95% CI, 0.32 to 1.55), respectively, for overall survival ( Pinteraction = .53). Results for the three end points were consistent in multivariable analyses adjusting for location of ILRR, prior CT, and interval from primary surgery. Conclusion The final analysis of CALOR confirms that CT benefits patients with resected ER-negative ILRR and does not support the use of CT for ER-positive ILRR.
Related Questions
What adjuvant systemic therapy would you give a patient with pN2 nodal relapse of ER+/HER2- breast cancer now s/p ALND, after initial mastectomy, adjuvant TC, and 5 years of endocrine therapy?
I'll give my thoughts, but appreciate others here as well. I'm assuming this patient is likely now post-menopausal, and also assuming that they had 5 years of endocrine therapy and then relapsed off of adjuvant therapy.I'm guessing the patient did not have radiation as they had a mastectomy and did ...
Do you start systemic therapy for patients with previously localized HR+ breast cancer developing solitary bone metastasis which is now triple negative if there are no other sites of disease after metastasis-directed radiation?
I would start chemotherapy because of the triple-negative status of the metastasis. This is a patient who initially presented with hormone receptor-positive breast cancer and subsequently developed an isolated bone metastasis that was triple negative. The question of systemic therapy post-localized ...
What systemic therapy would you recommend for axillary recurrence of triple negative secretory breast cancer previously treated with mastectomy alone?
The type of systemic chemotherapy for locoregional recurrence of triple negative breast cancer is not standardized. Based on the CALOR trial, the dealer's choice of systemic chemotherapy reduced the risk of breast cancer recurrence specifically in triple negative breast cancer. The patient has not r...
How would you treat a post-menopausal woman with recurrent breast cancer, T1bN0 HR+ (ER/PR > 90%), HER2- s/p lumpectomy and adjuvant RT with low oncotype of 6?
The question does not provide the details of recurrence as to whether this is a locoregional breast recurrence, with or without lymph node or chest wall involvement. Ipsilateral or contralateral or second primary? Prior lumpectomy margins, prior type, and extent of radiation therapy? Time to recurre...
In a patient with local recurrence of breast cancer after mastectomy, how would you sequence adjuvant treatment after wide local resection?
Endocrine therapy can be given simultaneously with RT without increasing toxicity or decreasing effectiveness, as shown in a randomized French-Swiss trial (Azria et al., PMID 20138810). Toxicities from chemotherapy may be greater and its effectiveness reduced (at least for high-risk patients) when g...
What is your preferred adjuvant chemotherapy regimen for a patient with local recurrence of TNBC two years after completing neoadjuvant ddAC-T who declined prior adjuvant capecitabine?
There is no clear data-driven option for a patient with TNBC local recurrence, although the underpowered CALOR study does support the use of chemotherapy in the local recurrence setting. I would offer this patient a taxane + carbo + pembro for 4-6 cycles if she doesn't have significant neuropathy. T...
Is there value to OncoType Dx and/or NGS testing for mutations such as ESR1 in patients who have ipsilateral isolated resectable skin recurrence in ER+ positive low Oncotype breast cancer 10 years after mastectomy and adjuvant AI for 5 years?
I would not order an Oncotype on this tumor if it is a delayed locoregional chest wall recurrence. These LRR events are at higher risk of distant disease and we don't have data on how prognostic or predictive the ODX score is in these scenarios. NGS is also of limited utility but may be helpful if a...
In which situations do you offer neoadjuvant chemotherapy for a nodal recurrence alone of ER/PR positive, HER2 negative breast cancer?
There is limited evidence to match this scenario on which to base the decision-making. On the one hand, this is a young woman who now has nodal disease. IF she had presented with this as her original diagnosis, the recommendation would have been for adjuvant chemotherapy followed by endocrine therap...
Which chemotherapy regimen would you recommend for locally recurrent TNBC several years after therapy with docetaxel + cyclophosphamide for four cycles?
Typical regimens for TN breast cancer include TC, AC-T, AC-TCb +/- Pembro, and CMF. The CALOR data supports using adjuvant chemotherapy for recurrence. Details that I would usually consider when selecting a regimen in this setting include: Does the patient have residual side effects or co-morbiditie...
Which systemic therapy (if any) do you offer premenopausal women with a second TNBC local resectable recurrence and an extensive chemotherapy history?
Patients with locoregional recurrence definitely benefit from repeated chemotherapy for sure (as shown in CALOR trial and our own experience). The question here is after exhausting anthracycline and taxane-based therapy as most patients would have been already, what might be the best regimen? The f...
What chemotherapy would you offer (if any) in a young patient after resection and radiation of a single site of metastatic PDL1 positive, triple negative breast cancer?
This is a challenging situation, as the patient is clearly at very high risk of developing other sites of metastatic disease but there is little data on the benefit of chemotherapy or immunotherapy in reducing that risk, delaying the development of metastatic disease, or improving survival. If the p...
How would you approach adjuvant endocrine therapy after excision of a hormone positive recurrence after mastectomy who finished 5 years of aromatase inhibitor for the same primary tumor in the context of NATALEE and MonarchE trials?
The key question is whether this is an endocrine-sensitive or endocrine-resistant disease. If this recurrence happened after discontinuation of endocrine therapy, then most likely it is because of withdrawing therapy that was effectively suppressing the disease. This is not an uncommon scenario, and...
How would you treat a locally recurrent triple negative breast cancer after achieving CR a year earlier to neoadjuvant ddAC-T, BCS and WBRT?
I would recommend staging work up to rule out distant metastases for this patient with high-risk TNBC before committing this patient to local therapy.Isolated Loco-regional recurrences (ILRR) are associated with a high risk of developing distant metastases and early recurrence (< 24 months, as in th...
How would you manage a postmenopausal female with a history of early stage invasive ductal ER+/HER2- breast cancer s/p mastectomy who has a local recurrence of ER+/Her2 - lobular carcinoma while on letrozole?
I am sure most of us would offer local resection and radiation therapy along with staging work up without consideration for chemotherapy given CALOR data showing no benefit in ER positive cases. The final analysis of CALOR does not support the use of chemotherapy for ER-positive isolated loco-region...
How would you approach a post-menopausal women with recurrent ER/PR+, HER2- breast cancer only in the axillary lymph nodes?
This sounds so characteristic of a low-grade ER+ tumor in an elderly lady. I would only resect and confirm at resection the above-suspected pathology. Clearly given her age indolent behavior, local recurrence and low volume I would not torture this elderly lady with nothing more than an AI. The prob...
How would you manage a patient with TNBC breast cancer with local recurrence at mastectomy site within 3 months of surgery?
Since the patient has not received any systemic therapy, and the recurrence occurred within 3 months of primary breast surgery, I would strongly consider chemotherapy followed by either surgical excision (if possible) or radiation to the site of local recurrence. CALOR trial provides some evidence f...
What chemotherapy regimen would you recommend to a patient with local regional recurrent ER negative, HER2 positive breast cancer who received TCH more than 5 years ago?
I would treat this patient with chemotherapy and anti Her-2 therapy. Her-2 positive disease has a higher risk of distant recurrence and as long as the primary tumor is >0.5 cm in size, I recommend chemotherapy with anti Her-2 therapy. The type of anti Her-2 therapy and chemotherapy will depend on th...
How would you treat isolated axillary recurrence of a previously node negative ER/PR+, HER2- breast cancer after prior neoadjuvant chemotherapy, lumpectomy/adjuvant RT, and adjuvant AI?
The problem of isolated local or regional recurrence has been a vexing one for years. There have been multiple attempts to complete a randomized trial with sufficient numbers to draw conclusions and none have succeeded. I was Principal Investigator for one such Intergroup trial in the 1980's closed ...
With the intent for cure, what neoadjuvant therapy would you give a patient with only chest wall recurrence 10 years after an advanced breast cancer was managed with mastectomy, ddAC and T, and 5 years of adjuvant endocrine therapy?
A chest wall recurrence is associated with high risk of metastatic disease either at time of diagnosis of the chest wall recurrence or over the next 5 years. Women who develop chest wall recurrences should be restaged. The approach to an isolated chest wall recurrence in this case is surgery with cl...
What adjuvant systemic therapy do you recommend for a pre-menopausal patient with a localized recurrence of ER+PR+HER2- invasive ductal carcinoma while on adjuvant ovarian suppression with an aromatase inhibitor?
I agree with the proposed plan to consider curative intent chemotherapy for local recurrence. However, I would consider changing her hormone therapy to a drug with a completely different mechanism of action such as tamoxifen as she may have an ESR mutation or some other biologic mechanism conferring...