Per the American Society of Clinical Oncology /College of American Pathologists (ASCO / CAP) guidelines:
Tumors with an immunohistochemical result of 2+ (equivocal):
HER2 / CEP17 ratio of > 2.0 and copy number of > 4.0 are considered positive
References
Wolff AC, Hammond MEH, Allison KH, Harvey BE, Mangu PB, Bartlett JMS, et al. Human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline focused update. J Clin Oncol. 2018;142(11):1364-1382.
Lin L, Sirohi D, Coleman JF, Gulbahce HE. American Society of Clinical Oncology/College of American Pathologists 2018 focused update of breast cancer HER2 FISH testing guidelines. results from a National Reference Laboratory. Am J Clin Pathol. 2019;152(4):479-485.
Can cause decrease in ejection fraction in up to 20% of patients:
Although this is often reversible
Trastuzumab:
Can less commonly cause pneumonitis
Pertuzumab:
Can cause rash and diarrhea
References
Gianni L, Pienkowski T, Im YH, Roman L, Tseng LM, Liu MC, et al. Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol. 2012;13(1):25-32.
Schneeweiss A, Chia S, Hickish T, Harvey V, Eniu A, Hegg R, et al. Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA). Ann Oncol.2013;24(9):2278-2284.
This regimen is associated with a high risk for febrile neutropenia (>20%)
References
Smith TJ, Bohlke K, Lyman GH, Carson KR, Crawford J, Cross SJ, et al. Recommendations for the use of WBC growth factors: American Society of Clinical Oncology Clinical Practice Guideline update. J Clin Oncol. 2015;33(28):199-212.
Citron ML, Berry DA, Cirrincione C, Hudis C, Winer EP, Gradishar WJ, et al. Randomized trial of dose-dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node positive primary breast cancer: first report of Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741. J Clin Oncol. 2003;21(8):1431-1439.
Showed a 3-year rate of survival free from invasive disease of:
98.7% for node negative tumors up to 3 cm in size:
With use of weekly paclitaxel / trastuzumab for 12 weeks followed by trastuzumab for 12 months
References
Tolaney SM, Barry WT, Dang CT, Yardley DA, Moy B, Marcom PK, et al. Adjuvant paclitaxel and trastuzumab for node-negative, HER2-positive breast cancer. New Engl J Med. 2015;372(2):134-141.
Tolaney SM, Guo H, Pernas S, Barry WT, Dillon DA, Ritterhouse L. Seven-year follow-up analysis of adjuvant paclitaxel and trastuzumab trial for node-negative, human epidermal growth factor receptor 2-positive breast cancer.J Clin Oncol. 2019;37(22):1868-1875.
Is found in up to 79.5% of patients on Palbociclib:
Neutropenia and the risk for infections:
Must be discussed with patients prior to initiation of treatment
Other common adverse effects of this drug include:
Fatigue (37.4%)
Nausea (35.1%)
Alopecia (32.9%)
References
Finn RS, Martin M, Rugo HS, Jones S, Im SA, Gelmon K, et al. Palbociclib and Letrozole in advanced breast cancer. New Engl J Med. 2016;375(20):1925-1936.
Finn RS, Crown JP2, Lang I3, Boer K4, Bondarenko IM5, Kulyk SO, et al. The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study. Lancet Oncol. 2015;16(1):25-35.
In the Suppression of Ovarian Function Trial (SOFT):
Ovarian function suppression given for 5 years:
Reduced disease-free survival (DFS) events when added to 5 years of adjuvant tamoxifen:
78.9% to 83.2% DFS at 8 years, hazard ratio (HR) of 0.76, P = .009
One-third of women entered in the SOFT trial were randomized to receive the aromatase inhibitor exemestane plus ovarian function suppression and they had an even better disease-free survival.
References
Francis PA, Pagani O, Fleming GF, Walley BA, Colleoni M, Lang I, et al. Tailoring adjuvant endocrine therapy for premenopausal breast cancer. N Eng J Med.2018;379(2):122-137.
Francis PA, Regan MM, Fleming GF, Lang I, Ciruelos E, Bellet M, et al. Adjuvant ovarian suppression in premenopausal breast cancer. N Engl J Med. 2015;372(5):436-446.
The use of an aromatase inhibitor (letrozole) with an inhibitor of the cyclin dependent kinases 4 and 6 (ribociclib):
Was compared with an aromatase inhibitor alone in postmenopausal women with hormone receptor positive HER2-negative metastatic breast cancer:
In the MONALEESA-2 study
MONALEESA-2 Trial:
Results showed an improvement with the addition of ribociclib to letrozole alone in:
Progression-free survival (PFS):
From 42.2% to 63%
Overall response rate:
From 37.1% to 52.7%
This regimen was also investigated in premenopausal women with advanced, hormone receptor-positive breast cancer, and improved PFS compared with placebo plus endocrine therapy
References
Hortobagi GN, Stemmer SM, Burris HA, Yap YS, Sonke GS, Paluch-Shimon S, et al. Ribociclib as first-line therapy for HR-positive, advanced breast cancer. N Engl J Med.2016;375(18)1738-1748.
Tripathy D, Im SA2, Colleoni M3, Franke F4, Bardia A5, Harbeck Nm et al. Ribociclib plus endocrine therapy for premenopausal women with hormone-receptor-positive, advanced breast cancer (MONALEESA-7): a randomised phase 3 trial. Lancet Oncol. 2018;19(7):904-915.
A mandibulotomy can be performed in one of three locations:
Lateral:
Through the body or angle of the mandible
Midline
Paramedian
A lateral mandibulotomy has several disadvantages:
First, the muscular pull on the two segments of the mandible is unequal:
Putting the mandibulotomy site under significant stress and causing a delay in healing:
For this reason, intermaxillary fixation may be required
Second, the ability to gain access to the suture line to maintain cleanliness following surgery in the oral cavity is hampered as a result of intermaxillary fixationleading to poor oral hygiene and the potential risk for sepsis of the suture line
Third, a lateral mandibulotomy poses several anatomic disadvantages including:
Denervation of the teeth distal to the mandibulotomy site and the skin of the chin:
As a result of transection of the inferior alveolar nerve
A lateral mandibulotomy also causes devascularization of the distal teeth and the distal segment of the mandible:
From its endosteal blood supply
The exposure provided by a lateral mandibulotomy:
Is limited
If the patient needs postoperative radiation therapy:
Delayed healing can lead to complications at the site of the mandibulotomy
For these reasons, a lateral mandibulotomy:
Is not recommended
By placing the mandibulotomy in the anterior midline:
All the disadvantages of a lateral mandibulotolotomy:
Are avoided
However, splitting the mandible in the midline:
Requires extraction of one central incisor tooth:
To avoid exposure of the roots of both central incisor teeth:
Which are at risk of extrusion
Extraction of one central incisor tooth alters the aesthetic appearance of the lower dentition
In addition, a midline mandibulotomy requires:
Division of muscles arising from the genial tubercle, that is:
The geniohyoid and genioglossus:
Leading to a delayed recovery of the functions of mastication and swallowing
Therefore a median mandibulotomy:
Also is not preferred for these reasons
A paramedian mandibulotomy:
On the other hand, avoids all the disadvantages of a lateral mandibulotomy and the sequelae of a midline mandibulotomy
It offers significant advantages, such as:
Wide exposure
Preservation of the geniohyoid and genioglossus muscles:
Leading to preservation of the hyomandibular complex
The only muscle requiring division is the mylohyoid muscle:
Which leads to minimal swallowing difficulties
A paramedian mandibulotomy:
Does not cause denervation or devascularization of the skin of the chin or the teeth and mandible
Fixation at the mandibulotomy site is easy
The site of the mandibulotomy is able to withstand radiation therapy if the patient needs postoperative treatment
Thus at present a paramedian mandibulotomy:
Remains an optimal surgical approach for access to posteriorly located larger lesions of the oral cavity and tumors of the oropharynx and parapharyngeal space
The latest National Comprehensive Cancer Network (NCCN) clinical practice guidelines:
Have added fluoroestradiol F18 (FES) PET scan to its list of considerations for patients with recurrent or metastatic ER breast cancer
The NCCN guideline now recommends clinicians consider the use of FES PET for ER-positive disease during work-up of patients with recurrent or metastatic breast cancer
The guideline update follows the publication of the Society of Nuclear Medicine and Molecular Imaging’s appropriate use criteria statement on ER-targeted PET imaging in March of 2023:
Which noted that FES PET is appropriate when a clinician is considering endocrine therapy and assessing ER status at initial diagnosis of metastatic breast cancer, when the disease progresses after endocrine therapy, when lesions are challenging or dangerous to biopsy, and / or when other tests evaluating ER status are inconclusive
The addition to FES PET in the NCCN guidelines in addition to fluorodeoxyglucose gives clinicians an opportunity to assess ER function in all tumor sites in patients with ER-positive metastatic breast cancer
FES was approved by the FDA for use as an adjunct to biopsy in patients with recurrent or metastatic breast cancer in May 2020 and is currently the only imaging agent approved by the agency for that indication:
This is a helpful tool for diagnostic confirmation and may have the ability to aid in prognosis and prediction of clinical benefit from endocrine based therapies, including with CDK 4/6 inhibitors
We have many endocrine options now, and FES PET may identify patients who remain ER+ and thus potentially benefit from endocrine based therapy
