Local breast cancer recurrence

Up to 10 to 15% of patients treated with lumpectomy and the whole breast irradiation, that is breast conservation therapy, will have a subsequent in-breast local recurrence.

Loco-regional recurrence after the mastectomy is variable related to patient characteristics, biologic nature of the tumor, lymph node involvement and treatments: patients with low to moderate risk of approximately 10% or less include older women and women with favorable tumor characteristics and no lymph node involvement, while moderate to high risk patients are less than 35 years of age, with stage III disease, with positive lymph nodes, with unfavorable tumor characteristics, and poor response to neoadjuvant chemotherapy.

The rate of local recurrence  varies with the hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status.



Local recurrence is lowest among patients with HR+, HER2– tumors and highest among those with triple‐negative tumors, regardless of whether the treatment includes BCT or mastectomy.



Among those with HR+, HER2– tumors, the risk of LR also varies significantly with the ((21‐gene Recurrence Score)).



LR can be observed even among the smallest cancers (microinvasive, T1a,b),16 and this indicates that this is a fundamental tumor characteristic and not one that is acquired over time. 

Postmastectomy radiation can reduce moderate to high risk patients to a low risk patient for loco-regional recurrence.

Postmastectomy radiation can reduce locoregional recurrence risk for clinically stage III disease, T3 tumors of high-grade, or for four or more positive lymph nodes, with adjuvant or neoadjuvant chemotherapy.

Patients with T4 tumors or N2-3 disease at presentation and patients with tumors of greater than 5 cm residual, and with four more positive lymph nodes following neoadjuvant chemotherapy will still have a local recurrence rate of 12 to 16%, even with postmastectomy radiation (Huang EH).

Salvage mastectomy is presently accepted as the standard of care for local recurrence after breast conservation therapy (BCT).

Salvage surgery in early studies associated with a survival rate of 50% or higher at five years, in BCT recurrent patients.

Up to one half of local recurrences are not associated with distant recurrence (Haffty BG, Millar EK).

Older women have a lower risk of ipsilateral recurrence of breast cancer than younger women, with or without radiation therapy, especially with small, hormone receptor positive tumors (Merchant TE,Hughes KS).

Outcome after local recurrence following BCT depends on various prognostic factors including: tumor size, histological subtype of recurrent disease, involvement of the skin and lymph nodes at the time of recurrence, location of the tumor, and the time interval between the first and second in-breast cancer diagnosis.

Patients with hormone receptor positive disease of the lower probability of recurring than patients with triple negative breast cancer

Patients that have had a longer interval between the two cancers have a better prognosis.

When a mastectomy is used to treat local recurrence after BCT the five year local control rate is 92% for recurrent disease occurring after five years and only 49% for patients with recurrent intervals of less than five years(Kurtz JM).

The National Surgical Adjuvant Breast and Bowel Project indicates that 25% of patients who have a loco-regional recurrence it will be an isolated metastasis(Taghian A).

New primary tumors, must be distinguished from original tumors, and lesions with differing histology since there is a statistically significant difference in the five-year survival new primary tumors vs. true recurrence at 89% and 36%, respectively (Haffty BG).

The mean time for a second cancer event is longer for a new primary compared to a true recurrence (Huang).

NKI70 gene test can identify subgroups of women within increased risk of local recurrence after breast conserving surgery and may predict for local recurrence after mastectomy(Nuyten DS).

In women younger than 50 years of age and the high Oncotype DX score have a greater than 35% chance of having a local-regional recurrence rate after mastectomy (Mamonouas E).

In a study by Huang there was a 77% survival rate among patients classified as having a new primary, similar to what is expected for similar stage disease at initial presentation: therefore the prognosis for second cancers are not uniformly associated with poor risk.

Salvage mastectomy has a reported local failure rate of less than 10% and a greater then 90% expected control rate for locally recurrent cancers.

Several factors influence outcome after local recurrence and include: tumor size, histologic subtype, skin involvement, nodal involvement, location of the recurrence in relation to the initially treated lesion, and the time interval between the primary and the recurrent lesion.

The use of a second lumpectomy alone, without radiation, after a local recurrence is associated with another local recurrence rate ranging from 19 to 50%.

In an evaluation of 57 patients treated with lumpectomy after local recurrence and a median follow-up time of 73 months the local recurrence rate was 19%, compared to 4% of patients that underwent salvage mastectomy(Salvadori).

Of 30 patients with local recurrence repeat lumpectomy resulted in nine patients having another local recurrence within three years(Komoike).

In a study of 747 patients that had ipsilateral breast recurrence after breast conservation surgery between 1998 and 2004 24% had a second lumpectomy and was found to have an inferior survival rate to that seen in women who had salvaged mastectomy(Chen).

Loco-regional recurrence maybe associated with synchronous metastatic disease.

In a study of 1057 patients who underwent mastectomy rate 93 patients developing loco-regional recurrence, 36% had synchronous distant metastases, and 33% developed distant disease during follow-up and 30% had isolated loco-regional recurrence(Buchanan CL).

In the SEER data review by Chen the women in the lumpectomy group were significantly older than in the mastectomy group and survival was improved when radiation followed the second lumpectomy.

Previously it was felt that application of radiation therapy to a previously irradiated tissue was contraindicated.

Newer studies indicate that partial breast brachytherapy is safe and effective treatment, following lumpectomy.

Today it is possible for partial breast irradiation with brachytherapy to treat a localized second in a previously irradiated breast.

Most partial breast irradiation techniques include three dimensional conformational external beam radiation, interstitial catheter, and intra-cavitary Mammosite brachytherapy.

The administration of 30 Gy by brachytherapy to previously irradiated breast tissue following recurrent local disease was associated with no major toxicities over one year follow-up (Chadha M).

The use of interstitial low-dose brachytherapy in patients with second lumpectomy and previous radiation using a dose of 45 to 55 Gy a 5 year actuarial survival was 87.9%, and the five-year mastectomy free survival rate was 94.4% (Chadna, Trombetta).

In general, the use of brachytherapy following second lumpectomy in patients with previously irradiated breasts provides good cosmetic results, high-level local control, and prevention of mastectomy.

In a group of 69 patients treated with second lumpectomy and low dose rate interstitial brachytherapy 14.6% of patients had local failures, and a five year overall survival rate of 91.8%, and a five-year freedom from second local recurrence and disease free survival of 77.4% and 68.9%, respectively (Hannoun-Levi).

In a study of 38 patients with local recurrence treated with salvage therapy with perioperative split course low dose interstitial brachytherapy and mean follow-up of 40 months 21% locally relapsed with a 55% 5 year survival rate (Maulard C).

Loco-regional recurrence rate for TRAM flap reconstructions among 419 cases was 3.8% with the meantime to recurrence of 1.6 years (Howard MA).

Loco-regional recurrence with TRAM flap occurs 50% of the time in the chest wall and 50% of the time in the skin flap, and 75% of patients were considered surgical candidates at the time of detection, but 56% of patients died from metastasis in need of 1.2 years after detection(Howard MA).

In a study of 155 patients with chest recurrences following mastectomy and a median follow-up of 62.1 months, patients with breast reconstructions had a slightly longer time to detection than patients without reconstruction although there was no impact in that 10 year actual overall survival(Laurent S).

In a study of locoregional recurrence rates in T1 and T2 beast cancers treated with modern surgical and adjuvant systemic treatments less than 3% have locoregional recurrence, signficantly lower rates than previously reported: 1019 patients with 0-3 positive nodes, median follow-up 7.5 years, no postoperative radiation was given (Kuerer HM).

In the above study only independent predictor of locoregional recurrence was age younger than 40 years at 10 years, with a LRR of 11.1% vs 3% for those older than 40 years (Kuerer HM).

In a study of 38 patients with isolated local relapses treated with low dose salvage brachytherapy and mean follow-up of 40 months 21% experienced a local relapse and overall 5 year survival rate was 55% (Maulard C et al).

Breast conserving therapy after local recurrence, without re-irradiation results in higher local failure rates than for those for repeat surgery and followed by repeat radiation therapy (Interstial) (Chadha M et al, Hannoun-Levi JM et al).

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