Author: Rodrigo Arrangoiz MS, MD, FACS, FSSO

• TNBCs arising in BRCA1 carriers have many similarities with sporadic basal-like tumors:
  • There being considerable overlap in tumor phenotypes
• Carriers of a deleterious BRCA1 mutation are more likely to have TNBCs than patients with sporadic cancers; in fact:
  • TNBC is the most common histologic subtype of breast cancer arising in BRCA1 mutation carriers
• The likelihood that breast cancer in a BRCA1 carrier will be of the TNBC variety is high according to numerous authors:
  • 56% to 87%
  • 60% to 80%
  • 69%
• Penault-Llorca and Viale report even higher rates:
  • Up to 90% of BRCA1-mutated tumors:
    • Being of the TNBC or basal type
  • For carriers of BRCA2, however:
    • Breast cancers are less likely to be TNBC:
      • 25%
• Another question posed by several researchers is, what is the likelihood of a patient with TNBC being the carrier of a deleterious genetic mutation?
  • Couch and colleagues examined the frequency of gene mutations in 1,824 patients with TNBC unselected for family history of breast or ovarian cancer:
    • Moreover, 8.5% had mutations of BRCA1 and 2.7% had mutations in BRCA2
  • Deleterious mutations in 15 other predisposition genes were detected in 3.7%, including:
    • PALB2, BARD1, RAD51D, RAD51C, and BRIP1
  • No mutations were found in CHEK2, CDH1, or STK11
  • The frequency of BRCA mutations varied according to the patient’s age:
    • Of all the deleterious mutations detected in Couch and colleagues’ cohort:
      • 38% were found in patients with TNBC diagnosed at the age of less than 40 years
• Wang and colleagues studied a group of 956 Chinese women with TNBC and found similar rates of BRCA1 and BRCA2 carrier status:
  • 7.1% and 2.3%, respectively
  • When examined by age, however, for patients aged 50 years or older:
    • The BRCA1 mutation rate was 10.5% compared with 3.7% for those aged older than 50 years
• BRCA1 mutation carrier status in patients with TNBC also varies by ethnicity:
  • In women of Ashkenazi Jewish descent with TNBC:
    • Up to 29% were BRCA1 mutation carriers
• Greenup and colleagues reported on 450 racially diverse patients with TNBC who had evaluable test results referred for genetic counseling to two academic hereditary cancer clinics:
  • Moreover, 30.8% patients carried a BRCA mutation, 23.5% BRCA1, 7% BRCA2, and one patient carried both BRCA1 and BRCA2
  • These authors also found differences in BRCA carrier status according to age and ethnicity:
    • In those patients diagnosed at less than 40 years of age, 44% were BRCA positive:
      • With majority being BRCA1 positive:
        • 84%, 54 patients
      • In that same age group 14% (nine patients) were BRCA2 positive
    • With regard to ethnicity, 20.4% of African American women were BRCA carriers, 20% of Hispanics, 33.3% of Caucasians, 28.5% of Asians, and

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A number of studies have found that obesity significantly increases the risk of both flap and donor complications. A meta-analysis also demonstrated that muscle-sparing abdominal flaps resulted in a lower pooled incidence of flap loss and fat necrosis.

While radiation is associated with higher wound healing complications with reconstruction, the rate of complications is similar whether reconstruction precedes or follows radiation.

Complication rates of immediate autologous reconstruction are similar between those taking neoadjuvant chemotherapy and those who do not.

There are no significant differences in the rate of chest wall recurrence after mastectomy whether a skin-sparing procedure with immediate reconstruction is performed or not.

Kelley BP, Ahmed R, Kidewll KM, Kozlow JH, Chung KC, Momoh AO. A systematic review of morbidity associated with autologous breast reconstruction before and after exposure to radiotherapy: are current practices ideal? Ann Surg Oncol. 2014;21:1732-1738.

Lee KT and Mun GH. Effects of obesity on postoperative complications after breast reconstruction using free muscle-sparing transverse rectus abdominis myocutaneous, deep inferior epigastric perforator, and superficial inferior epigastric artery flap: A systematic review and meta-analysis. Ann Plast Surg. Epub ahead of print December 19, 2014; doi: 10.1097/SAP.0000000000000400.

Patients with hyperparathyroidism may develop kidney stones or nephrocalcinosis (deposition of calcium salts in the renal parenchyma). Over time, the renal effects may result in a decline in renal function. In some patients, the diagnosis of hyperparathyroidism is a direct result of a work-up in those initially presenting with calcium-containing stones. Read more at :https://arrangoizmd.com/2022/07/22/kidney-disease-and-hyperparathyroidism/

The ideal margin width after mastectomy has been debated, but the definition of a negative margin for invasive cancer as used in the National Surgical Adjuvant Breast and Bowel Project (NSABP) trials and recommended in the recent SSO Consensus Panel was no invasive tumor at the inked margin. Other randomized trials did not specify margin status or used grossly negative.

A recent consensus conference sponsored by the SSO, ASTRO, and CAP reviewed the literature and concluded that no tumor on ink is an adequate margin for breast-conserving surgery and radiation.

Shave margins appear to be the most efficient way to examine margin status and determine need for reoperation.

The width of margins for ductal carcinoma in situ (DCIS) is more hotly debated.

A patient treated with BCS and a pathology report showing a T2N0(i+) breast malignancy that is triple negative should be evaluated in a multidisciplinary approach, so a medical oncologist and a radiation oncologist are important in the evaluation of this patient. Even if the patient chose to have mastectomy, a referral to a medical oncologist is indicated. Isolated tumor cells are not a reason to perform ALND.

ER(-) patients should not have Oncotype testing. Patients with node-negative, ER-positive cancer are the most likely to benefit from multigene expression-based prognostic tests. In contrast, adjuvant chemotherapy remains a standard recommendation for patients with T2N0 cancers that are ER-negative, PR-negative, and HER2-negative or are HER2-positive.

Several multigene prediction assays are commercially available (Oncotype Dx; Mammaprint, and PAM50), but only Oncotype Dx has level 1B evidence to support its use in predicting benefit of adjuvant chemotherapy. This genomic profile was tested using tumor tissue from patients treated on a randomized clinical trial comparing tamoxifen to tamoxifen plus chemotherapy. The other genomic assays provide good prognostic information but were not well validated. However, clinical trials are underway to validate each of these tests in randomized patient samples. The decision to order a multigene assay test is usually left to the medical oncologist to determine whether or not the test is indicated. If a patient is not willing to accept a recommendation of adjuvant chemotherapy, the information from the test will not be useful.

At times a surgeon can order the multigene assay so that the information is available to the oncologist at the time of the visit, but it is important that the surgeon and medical oncologist communicate as to which patients should have this test performed so that the information is useful to the patient and the multidisciplinary team.

Chagpar AB, Killelea BK, Tsangaris TN, et al. A randomized, controlled trial of cavity shave margins in breast cancer. N Engl J Med. 2015;373:503-510.

Gangi A, Chung A, Mirocha J, Liou DZ, Leong T, Giuliano AE. Breast-conserving therapy for triple-negative breast cancer. JAMA Surg. 2014;149:252-258.

Giuliano AE, Hawes D, Ballman KV, et al. Association of occult metastases in sentinel lymph nodes and bone marrow with survival among women with early-stage invasive breast cancer. JAMA. 2011;306:385-393.

Meattini I, Desideri I, Saieva C, et al. Impact of sentinel node tumor burden on outcome of invasive breast cancer patients. Eur J Surg Oncol. 2014;40:1195-1202.

Moran MS, Schnitt SJ, Giuliano AE, et al. Society of Surgical Oncology-American Society for Radiation Oncology consensus guideline on margins for breast-conserving surgery with whole-breast irradiation in Stages I and II invasive breast cancer. Ann Surg Oncol. 2014;21:704-716.

A number of studies have found that lifting weights reduces the development of lymphedema.

It is also clear that air travel (whether long or short haul) does not increase the risk of lymphedema>

Sleeves are not indicated unless there is established lymphedema.

A Cochrane review found no increase in lymphedema associated with early shoulder-mobilization exercises (within 7 days of surgery), and in fact found that these were better than delayed exercises.

Weight loss, whether through reducing calories or fat intake, has been found to result in reduced lymphedema.

Studies have found that patients with a prior axillary dissection could undergo elective hand surgery (including carpal tunnel surgery) without an increase in lymphedema rates.

References:

Brown JC, Schmitz KH. Weight lifting and physical function among survivors of breast cancer: a post hoc analysis of a randomized controlled trial. J Clin Oncol. 2015;33:2184-2189.

Kilbreath SL, Ward LC, Lane K, et al. Effect of air travel on lymphedema risk in women with history of breast cancer. Breast Cancer Res Treat. 2010;120:649-654.

Stuiver MM, ten Tusscher MR, Agasi-Idenburg CS, Lucas C, Aaronson NK, Bossuyt PM. Conservative interventions for preventing clinically detectable upper limb lymphedema in patients who are at risk of developing lymphedema after breast cancer therapy. Cochrane Database Syst Rev. 2015;2:CD009765.