Breast conservative therapy (BCT)

Implies complete removal of breast cancer with a concentric margin of surrounding normal tissue in a cosmetically acceptable manner.

Surgical evaluation of the axilla is usually part of the surgical approach.

The presence of pathologically involved lymph nodes does not contraindicate the procedure.

Has a long-standing and successful track record as state-of-the-art management in early-stage invasive breast cancer, a disease that currently is often screen detected in middle-aged and elderly, and often postmenopausal women.

Survival rates after breast conserving surgery followed by radiation are similar to results after mastectomy in invasive breast cancer.

Breast conserving surgery followed by radiotherapy is as effective as mastectomy for the treatment of breast tumors up to 5 cm.

Breast conserving surgery generates staging information without burning any bridges, and has other advantages compared with a potential premature decision to pursue mastectomy.

BCT is contraindicated for patients who are pregnant and would require radiation during pregnancy, have diffuse suspicious or malignant appearing micro calcification on mammography, have widespread disease that cannot be incorporated by local excision of a single region of segment of breast tissue with satisfactory cosmetic results, have diffusely positive pathologic margins, or have homozygous for ATM mutation.

Relative contraindications to lumpectomy include previous RT to the breast or chest wall, active connective tissue disease involving the skin, persistently positive pathologic margin, or those known or suspected to have genetic predispoition to breast cancer that may have an increased risk of ipsilateral breast recurrence or contralateral breast cancer with BCT or considered for prophylactic bilateral mastectomy for risk reduction for known suspected syndrome Li-Fraumeni syndrome.

Negative margin width when the tumor is not present on ink is considered adequate for BCT followed by radiotherapy.

A positive margin after breast conserving surgery is defined as ink on tumor.

Patients with positive ink on tumor findings require further surgery,either a re-excision to achieve negative margins or a mastectomy.

Breast size and volume of excised tissue are important considerations in BCT.

With relatively large breasts, residual tissue is sufficient to obtain satisfactory cosmetic outcomes.

With small to moderate-sized breasts, the volume displacement surgical technique can be performed after the removal of defects less than 50 g in mass.

If the defects are greater than 50 g, satisfactory cosmetic outcome can only be obtained using volume replacement techniques.

The National Surgical Adjuvant Breast and Bowel Project B-06 trial (NSABP B-06) 20 year follow-up showing overall survival of 46% and 47% for breast conservation therapy and mastectomy, respectively, and 20 year local recurrence rate 8.8%, and 2.3% respectively (Fisher B et al).

In the National Surgical Adjuvant Breast and Bowel project B-06 trial and in the Milan Cancer Institute trial, women with early breast cancer treated with breast conservative therapy and postoperative radiotherapy to the ipsilateral breast had higher rates of local recurrence but similar long-term survival when compared with those undergoing radical mastectomy.

In a study of 1326 women, the omission of irradiation included women, 65 years of age or older, who at hormone receptor, node negative, T1 or T2 primary breast cancer: there was an increased incidence of local recurrence, but had no detrimental effect on this recurrence is the first event, or overall survival among women 65 years of age or older, with low risk, hormone receptor, positive early breast cancer ( Kunkler, IH).

Despite equivalence of mastectomy and BCT for primary treatment of breast cancer the rate of mastectomy has been increasing in recent years.

Young age is a significant predictor of an increased likelihood of ipsilateral breast cancer recurrence after BCT.

Early Breast Trialists’ Collaborative Group meta-analysis and overview of randomized trials of locoregional treatment with more than 7000 women randomly assigned after breast sparing surgery (lumpectomy) to receive RT or not, and 8 clinical trials with more than 4000 women, randomly assigned to mastectomy versus BCT plus RT: no difference in breast cancer mortality or overall survival for patients randomized to mastectomy compared with breast conserving surgery plus RT, addition of RT to breast conserving surgery was associated with a 21.7% reduction in 10 yr local recurrence rate, a 5.4% reduction in 15 year breast cancer mortality and a 5.3 % reduction in 15 year overall mortality(Clarke M).

Early Breast Cancer Trialists Collaborative Group showed that breast irradiation reduced ipsilateral breast tumor recurrence from 29 to 10% in patients with node negative disease and from 47% to 13% in patients with node positive disease.

This study indicated that local control and prevention of one local recurrence at five years prevents one death from breast cancer in 15 years.

Whole breast irradiation (WBI) after BCT is the standard approach, since the risk of recurrence in the ipsilateral breast can be as high as 20% or more, even in node-negative women.

Standard whole breast radiotherapy is considered the safest approach to avoid ipsilateral in breast recurrence.

Whole breast irradiation plus regional nodal irradiation significantly improved disease free survival, but not overall survival, in a randomized, multicenter phase 3 trial of women with node positive or high risk, node negative disease treated with WBI: at 5 years more local recurrences occurred among chemotherapy first group and more distant metastases in the radiation first group, however at ten years the patterns of first failure were not significantly different.

In the above study patients treated with chemotherapy first with close margins had a substantial risk of local recurrence that was not seen in the radiation first treated group, and patients with positive margins had a high local recurrence rate independent of treatment sequence.

Solitary lesions <4cm in diameter are generally considered appropriate for BCT approach.

Locoregional recurrence in mastectomy patients treated for breast cancer typically have a grim prognosis but most recurrences after breast conserving surgery occur at the original site of the tumor and can be salvaged by additional surgery, with a median survival rate of 69% at 5-year follow-up.

22% of patients have at least one episode of inflammation or infection of the breast.

Not considered a treatment option with multiquadrant disease since patients may have local recurrences of 40% or higher.

No differences in rates of recurrence after BCT among various histologic types of invasive breast cancer.

Because of infiltrative growth patterns and frequent discontinuity it is,however, more difficult to get clear margins in patients with lobular carcinoma.

The presence of centrally located tumors involving the subareolar tissue andor nipple was previously considered a relative contraindication to breast conserving surgery because of the need for nipple removal.

However, if disease is confined to a central unifocal area, without diffuse microcalcifications, and if margin negativity can be achieved, performing a central segmentectomy is reasonable.

Long-term follow-up studies reveal that ipsilateral breast tumor recurrence after BCT is 9-15% or 0.5-1% per year in invasive breast cancer.

20 year cumulative incidence of ipsilateral relapse was 15% in the age group 40 years or younger, and in 14% and 41-50-year-old women.

In the above study 18% and 90% ipsilateral recurrence was seen in tumors with and without ductal carcinoma in situ.

Risk for local recurrence include young age, positive margins, multicentric disease, high grade,and vascular invasion.

Luminal tumor types are less likely to recur locoregionally than HER2 positive or triple negative tumors.

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).

Use of chemotherapy is associated with increased ipsilateral breast tumor recurrence-free survival rates in patients less than 50 years of age.

Extensive intraductal component (EIC) of little importance if negative margins can be obtained.

Tumor cells at the margins of a lumpectomy are associated with a higher rate of local failure than with negative margins.

One report revealed that ipsilateral tumor recurrence at 8-years was 7%, 14% and 27% for negative and close margins, focally positive and extensively positive margins, respectively indicating the importance of margin status in IBTR.

Large resections are the best predictor of fair to poor cosmetic outcomes.

In situ tumors have an increased risk of local recurrence than do infiltrating ductal cancers.

Relative risk of ipsilateral breast cancer recurrence is 3.0 without radiation therapy and improvement in local control associated with an 8.6% improvement in overall survival, indicating that locally recurrent disease is a nidus for distant metastases not present at the time of initial treatment.

Patients with primary invasive breast cancer <2cm diameter, grade 1 and node negative, treated by wide local excision (WLE) with clear margins were randomised into a 2×2 clinical trial of factorial design with or without radiotherapy and with or without tamoxifen: The actuarial breast cancer specific survival in 1135 randomised patients at 10years was 96%, local recurrence was reduced in patients randomised to radiotherapy (HR) and to tamoxifen (HR 0.33), and LR after WLE alone was 1.9% per annum versus 0.7% with RT alone and 0.8% with tamoxifen alone (Blamey RW et al),

In the above study no patient randomised to both adjuvant treatments developed LR, and LR at 2.2% per annum for surgery alone versus 0.8% for either adjuvant radiotherapy or tamoxifen and 0.2% for both treatments.