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Adding E-602 to cemiplimab demonstrated anti-tumor effects in patients PD-L1–resistant solid cancers. 

Novel Drug Combo Is Promising for PD-L1-Resistant Solid Cancers

Mitazalimab combined with mFOLFIRINOX led to responses and survival benefits in patients with metastatic pancreatic ductal adenocarcinoma. 

Mitazalimab Plus mFOLFIRINOX Improves Survival in Pancreatic Cancer

The novel drug SHR-A1921 was safe and efficacious in patients with platinum-resistant ovarian cancer, according to phase 1 data. 

Novel ADC Shows Promise in Platinum-Resistant Ovarian Cancer

Docetaxel was associated with lower rates of peripheral neuropathy compared with paclitaxel for Black patients with breast cancer. 

Chemo Should be Tailored to Decrease Neuropathy in Black Patients

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®. Gina joined the company in 2015 and has held various positions on 

Prior to joining MJH Life Sciences, she worked at Gannett as a full-time reporter with the Asbury Park Press. Email: gmauro@onclive.com

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Approximately one-third of patients with pancreatic cancer and anxiety had a palliative care consultation, data showed. 

Palliative Care Is Underutilized, May Boost Mental Health in Pancreatic Cancer

The FDA granted an accelerated approval to zanidatamab-hrii for previously treated, unresectable or metastatic HER2-positve biliary tract cancer. 

FDA Approves Zanidatamab for Pretreated HER2-Positive Biliary Tract Cancer

The FDA granted a fast track designation to ALE-P02 for patients with CLDN1-positive squamous solid tumors. 

FDA Fast Tracks ALE.P02 for CLDN1-Poisitive Solid Cancers

Clinicians should consider a rapid taper approach for patients with cancer who exhibit repeated signs of opioid misuse, an expert said. 

Rapid Taper Plays Role in Suspected Opioid Misuse in Patients With Cancer

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While patients may feel a sense of urgency in making a treatment decision, it’s important for patients to assess their own feelings about their goals for treatment.

Your Treatment Plan: What You Need to Know

Attempting to learn and process large amounts of complex information after a diagnosis of pancreatic cancer can leave anyone feeling lost. So where should you turn? Start with Patient Central.

How to Navigate Pancreatic Cancer Resources

Getting organized can help patients and their loved ones take control and better understand their options after a cancer diagnosis.
 

10 Tips to Help You Get Organized After Diagnosis

The new CAR-T cell therapy, anitocabtagene autoleucel (anito-cel), may offer another option beyond ciltacabtagene autoleucel (cilta-cel; Carvykti) for the treatment of patients with relapsed/refractory multiple myeloma, according to a data preview from the phase-2 iMMagine-1 trial (NCT05396885) trial released by Gilead Sciences and Arcellx.

Findings showed that per International Myeloma Working Group (IMWG) criteria, the investigator-assessed overall response rate (ORR) was 95% with a complete/stringent response rate of 62%. A total of 92% of eligible patients were minimal residual disease-negative, at least to the level of 10-5.

Kaplan-Meier-estimated 6-month progression-free survival (PFS) was 90% (95% CI, 77%-96%), and overall survival (OS) was 95% (95% CI, 85%-98%).

The median page age was 66 years, and the median follow-up was 10.3 months. Additionally, patients had received a median of 4 lines of therapy, with 45% having only 3. Of note, 69% of patients were triple-class refractory and 34% were penta-class refractory.

“Preliminary results from the first 58 patients in the phase 2 iMMagine-1 study demonstrate deep and durable responses and manageable safety in a high-risk fourth line or higher (4L+) [relapsed/refractory multiple myeloma] population including triple- and penta-class refractory disease,” the press release stated.1 “Notably, no delayed neurotoxicities, including no cranial nerve palsies, Guillain-Barré syndrome, or Parkinsonian-like symptoms have been observed with anito-cel to date.”

However, the FDA has previously placed a clinical hold on the phase 2 iMMagine-1 trial in June 2023 following a patient death that investigators attributed to limitations of the bridging therapy.

The hold was subsequently lifted in August 2023 after an investigation revealed that the death was a result of a patient who was treated with anito-cel after becoming ineligible for treatment under trial protocol before infusion with the drug and was treated in a manner that conflicted with the study’s protocol.

 The FDA approved dosing of all 17 patients enrolled in the trial prior to the partial clinical hold but had not yet been dosed before the hold, which reduced disruption of the treatment.

Following the hold lift, the FDA and the developer agreed on modifications to the trial’s protocol regarding the prevention and management of adverse effects (AEs). The FDA also permitted an expanded list of bridging options for patients enrolled in the iMMagine-1 trial to better align with current clinical practice.

In 46 patients, either no cytokine release syndrome (CRS; 16%) or grade 1 CRS (64%) was observed. For 31 patients, no fever or CRS appeared in the first 4 days of anito-cel treatment.

Regarding AEs, 3 deaths occurred due to retroperitoneal hemorrhage, CRS, and fungal infection. To date, no other therapy-related deaths or grade 3 or higher CRS/immune effector cell-associated neurotoxicity (ICAN) events have taken place. Of grade 3 or higher AEs, cytopenia was the most common treatment-emergent AE; 36 patients had neutropenia, 15 had anemia, and 15 had thrombocytopenia.

Inclusion criteria included being age 18 years or older; relapsed/refractory multiple myeloma treated with at least 3 prior regiments of systemic therapy including immunomodulatory drugs (IMiD), proteasome inhibitor, and anti-CD-38; an ECOG performance score of 0 or 1; and documented measurable disease including serum M-protein, urine M-protein, and involved serum free light chain; amongst other requirements.

Exclusion criteria were history of plasma cell leukemia; treatment with high-dose systemic steroid therapy, gene therapy, prior B-cell maturation antigen directed therapy, or autologous stem cell transplantation within 3 months to treatment; severe or uncontrolled intercurrent illness/laboratory abnormalities; and contraindication to fludarabine or cyclophosphamide; among other things.

More complete findings from the iMMagine-1 trial are to be reported at the 

2024 American Society of Hematology Annual Meeting

1. Arcellx to present clinical data for its phase 1 and iMMagine-1 studies in patients with relapsed or refractory multiple myeloma at the 66th ASH Annual Meeting and exposition and announces progress in iMMagine-3 study. News release. Arcellx, Inc. November 5, 2024. Accessed November 7, 2024. https://tinyurl.com/2u9cak8x

2. Arcellx announces clinical hold for its IMMagine-1 phase 2 clinical program. News release. Arcellx, Inc. June 19, 2023. November 7, 2024. bit.ly/3NCXBKz

3. Arcellx announces partial clinical hold lifted on IMMagine-1 phase 2 clinical program and reports second quarter financial results. News release. Arcellx. August 14, 2023. Accessed November 7, 2024. https://tinyurl.com/yd7zz2c2

Anitocabtagene autoleucel may be a promising CAR-T cell therapy option for patients with relapsed/refractory myeloma. 

Anito-Cel Shows 95% OS Rate in Relapsed/Refractory Myeloma

Patients with hormone receptor (HR)-poisitive, HER2-low or -ultralow metastatic breast cancer (MBC) who were treated with Trastuzumab deruxtecan (T-DXd; Enhertu) tended to have less deterioration in physical/role functioning and pain compared with those who were treated with a treatment of physician’s choice (TPC), according to data presented at the 2024 

European Society for Medial Oncology (ESMO) Congress

Findings were discovered via an analysis of patient-reported outcomes (PROs) on quality of life from the DESTINY-Breast06 trial (NCT04494425). Data showed a similar median time to deterioration (TTD) overall between the 2 arms in the intent-to-treat (ITT) population and the HER2-low subgroup, but differences in some symptoms. The median time to pain deterioration showed the most significant improvement for T-DXd at 22.0 months (95% CI, 17.2-not reached) vs 6.3 months (95% CI, 4.8-9.6) for TPC (HR, 0.51; 95% CI, 0.39-0.65).

“The global health/QOL was observed over 31 weeks for both arms. The QOL scores did not change from the baseline to a clinically significant degree,” Xichun Hu, MD, PhD, of the department of medical oncology in Fudan University Shanghai Cancer Center and professor in the department of oncology at Shanghai Medical College at Fudan University in Shanghai, China, said in his presentation. “Time to deterioration in QOL was similar with the 2 treatment arms. T-DXd reduced the risk of clinically meaningful deterioration in pain by 49%.”

The multicenter, open-label, randomized phase 3 DESTINY-Breast06 trial investigated the HR+, HER2-low population, defined as HER2 immunohistochemistry [IHC] 1+ or IHC 2+/in situ hybridization [ISH]-negative, as well as in patients with HR+, HER2-ultralow disease, defined as HER2 IHC 0 with membrane staining. The prior lines of therapy received by patients in this study included at least 2 lines of endocrine therapy with or without targeted therapy for MBC or those who had disease progression within 6 months of starting first-line endocrine therapy and CDK4/6 inhibitor therapy for MBC or recurrence within 24 months after starting adjuvant endocrine therapy.

Patients were randomly assigned on a 1:1 basis to receive 5.4 mg/kg T-DXd every 3 weeks or TPC chemotherapy including capecitabine, nab-paclitaxel, or paclitaxel.

In the primary analysis of the trial, investigators reported that it met its primary end point of progression-free survival per blinded independent central review (BICR) assessment with T-DXd showing 13.2 months compared with 8.1 months for TPC (HR, 0.62; 95% CI, 0.51-0.74; 

The patient-reported outcomes were assessed for both the ITT population (n = 436 for T-DXd and n = 430 for TPC) and the HER2-low group (n = 359 and n = 354, respectively).1 The median duration of treatment was 11.0 months with T-DXd vs 5.6 months with TPC chemotherapy. The European Organisation for Research and Treatment of Cancer QLQ-C30 oncology-specific questionnaire and the QLQ-BR45 breast cancer­–specific questionnaire were assessed at baseline, every 3 weeks until the end of treatment, and then every 3 weeks until second progression or death.

The QLQ-C30 evaluated Global Health Status (GHS)/QOL, physical, emotional, role, social, and cognitive functional scales, and symptom scales. Hu reported that overall GHS/QOL were maintained over 31 weeks with T-DXd and TPC in the ITT population, with a mean baseline GHS score of 69.51 and 65.88, respectively. With a mean change of 10 points from baseline being considered meaningful, neither arm showed any significant shifts over time with 65.8% compliance in the T-DXd arm and 69.8% in the TPC arm. Median time to deterioration in GHS/QOL was 11.3 months (95% CI, 8.3-14.7) for T-DXd and 10.5 months (95% CI, 7.7-13.3) for TPC (HR, 0.93; 95% CI, 0.73-1.18).

In terms of pain, T-DXd significantly reduced the risk of deterioration per QLQ-C30. It also reduced risk of deterioration in several other outcomes including physical functioning (HR, 0.72; 95% CI, 0.56-0.92), role functioning (HR, 0.75; 95% CI, 0.60-0.94), emotional functioning (HR, 0.71; 95% CI, 0.53-0.95), and fatigue (HR, 0.76; 95% CI, 0.61-0.93). T-DXd was worse than TPC in nausea/vomiting (HR, 1.60; 95% CI, 1.28-2.02), appetite loss (HR, 1.33; 95% CI, 1.05-1.69), and constipation (HR, 1.74; 95% CI, 1.34-2.27).

The QLQ-BR45 evaluated multi-item scores including skin mycosis symptoms, body image, sexual functioning, arm symptoms, and breast symptoms. The TPC arm showed a clinically meaningful deterioration based on this measure, reaching a 10-point adjusted mean change from baseline at approximately 7 weeks and continuing to show 10 or more points difference through 31 weeks. However, the T-DXd arm did not differ significantly from baseline. “Among the components in the BR45 questionnaire, clinically meaningful deterioration of skin and mucosal system was observed with TPC, but not with T-DXd,” said Hu.

He emphasized that with a duration of treatment approximately double that of TPC, T-DXd maintained QOL as well as delaying time to deterioration in some areas. “Gastrointestinal [GI] symptoms reported by patients who receiving T-DXd highlight the importance to implementing antiemetic prophylaxis in the clinic. Further investigation of the effect of antiemetic prophylaxis on GI symptoms and associated QOL in patients receiving T-DXd is warranted,” said Hu.

He added that the GI adverse events reported in the QOL data “did not appear to be detrimental to overall preservation of QOL and were consistent with the safety profile reported by study investigators.”

“PRO results describing patients’ perspective further support T-DXd as a new therapeutic option following 1 or more endocrine-based therapies for patients with HER2-low and HER2-ultralow, HR+ MBC,” he concluded.

1. Hu X, Curigliano G, Yonemori K, et al. Effects of trastuzumab deruxtecan (T-DXd) vs choice of chemotherapy (TPC) on patient-reported outcomes (PROs) in hormone receptor-positive, HER2-low or HER2-ultralow metastatic breast cancer (mBC): Results from DESTINY-Breast06. Presented at: 2024 ESMO Congress; September 13-17, 2024; Barcelona, Spain. Abstract LBA22.

2. Curigliano G, Hu X, Dent RA, et al. Trastuzumab deruxtecan (T-DXd) vs physician’s choice of chemotherapy (TPC) in patients (pts) with hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-low or HER2-ultralow metastatic breast cancer (mBC) with prior endocrine therapy (ET): primary results from DESTINY-Breast06 (DB-06). 

 2024;42(suppl 17):LBA1000. doi:10.1200/JCO.2024.42.17_suppl.LBA1000

Trastuzumab deruxtecan improved time to deterioration for pain and other categories, in patients with HER2 low/ultralow breast cancer.

T-DXd Outranks Treatment of Physicians’ Choice in QOL for HR+/HER2-Low/Ultralow MBC

The FDA approved inavolisib (Itovebi) plus palbociclib (Ibrance) and fulvestrant for the treatment of endocrine-resistant, 

-mutant, hormone-receptor (HR)-positive, HER2-negative locally advanced or metastatic breast cancer that is determined by an FDA-approved test. The indication is specifically for patients who experienced recurrence on or after adjuvant endocrine therapy.

The approval is based on findings from the randomized, double blind INAVO120 trial (NCT04191499), which included 325 patients whose disease progressed within 12 months of completing adjuvant endocrine therapy and who did not have prior systemic therapy for locally advanced or metastatic disease.

Researchers defined primary endocrine resistance as relapse within the first 2 years of adjuvant endocrine therapy, while secondary endocrine resistance was relapse while on adjuvant endocrine therapy after 2 or more years or relapse within 12 months of completing endocrine therapy.

Patients were randomly assigned 1:1 to receive an oral dose of either 9 mg of inavolisib or a placebo once per day, alongside 125 mg of daily palbociclib and 500 mg of fulvestrant administered on days 1 and 15 during cycle 1, followed by day 1 of every 28-day cycle thereafter. Participants continued treatment until disease progression or unacceptable toxicity.

The primary end point of the trial was progression-free survival (PFS) per RECIST version 1.1. Median PFS was 15.0 months (95% CI, 11.3-20.5) in the inavolisib arm and 7.3 months (95% CI, 5.6-9.3) in the placebo arm (hazard ratio, 0.43; 95% CI, 0.32-0.59; 

Secondary end points were overall survival (OS), investigator-assessed objective response rate (ORR), and duration of response (DOR).

Median DORs were 18.4 months (95% CI, 10.4-22.2) and 9.6 months (95% CI, 7.4-16.6), respectively. Meanwhile, the ORR was 58% (95% CI, 50%-66%) in the inavolisib-containing arm and 25% (95% CI, 19%-32%) in the placebo arm.

An interim analysis of OS did not reach statistical significance but was supportive of the overall benefit risk assessment with the addition of inavolisib, reducing the risk for death by 36% (hazard ratio, 0.64; 95% CI, 0.43-0.97).

The most common adverse events (including laboratory abnormalities) that occurred in 20% or more of patients were: decreased neutrophils, decreased hemoglobin, increased fasting glucose, decreased platelets, decreased lymphocytes, stomatitis, diarrhea, decreased calcium, fatigue, decreased potassium, increased creatinine, increased ALT, nausea, decreased sodium, decreased magnesium, rash, decreased appetite, COVID-19 infection, and headache.

FDA news release. FDA approves inavolisib with palbociclib and fulvestrant for endocrine-resistant, PIK3CA-mutated, HR-positive, HER2-negative, advanced breast cancer. October 10, 2024. Accessed October 10, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-inavolisib-palbociclib-and-fulvestrant-endocrine-resistant-pik3ca-mutated-hr-positive

Inavolisib plus palbociclib and fulvestrant was approved for the treatment of PIK3CA-mutant, HR-positive, HER2-negative locally advanced or metastatic breast cancer. 

FDA Approves Inavolisib Regimen for PIK3CA-mutated, HR+, HER2— Breast Cancer 

Pregnant patients with breast cancer tend to have favorable prognoses and low adverse obstetric and perinatal outcome risks, according to data from 3 studies that assessed risk factors associated with higher cancer incidences in Swedish women. Findings were outlined in a news release from Karolinska Institutet.

Acta Obstetricia et Gynecologica Scandinavica

 found that pregnancy-associated cancer (PAC) rates increased by age, with women ages 15 to 19 at the lowest for PACs (5.3 cases per 100,000) and women ages 40 to 44 at the highest risk (63.5 cases per 100,000).

 Additionally, preterm deliveries were more common among women with PAC during pregnancy (30.6%) vs all deliveries (5.3%) or PAC within 1 year following delivery (8.1%).

Investigators of this study found that crude incidence rates of pregnancy-associated cancer increased significantly from 21.3 per 100,000 between 1980 and 1984 to 38.2 per 100,000 from 2010 to 2014. Additionally, crude incidence increased over all time periods and trimesters, most notably first-year post-delivery. Significant associations were observed between both increasing maternal age and later trimesters and pregnancy-associated cancer rate.

Immigrant background was significantly associated with lower pregnancy-associated cancer rates for any tumor type (incidence rate ratio [IRR], 0.76; 95% CI, 0.64-0.91; 

 = .0025), but not for breast cancer (IRR, 0.88; 95% CI, 0.60-1.29; 

 = .5071). Additionally, smoking was significantly associated with a higher pregnancy-associated cancer risk (IRR, 1.28; 95% CI, 1.07-1.54; 

 = 0.0069), most notably for cervical cancer (IRR, 2.32; 95% CI; 1.52-3.54; 

Investigators utilized Swedish birth and cancer registers from 1973 to 2017 to identify all cases of women with pregnancy-associated cancers ages 15 to 44 in the population-based cohort study. The study only included first occurrences of cancer in each woman and in the group of women without cancer, only deliveries free of maternal cancer history were included.

Of deliveries among women with breast cancer evaluated in another study published in 

, 42.6% were planned preterm (relative risk [RR], 67.1; 95% CI, 33.2%-135.6%), and 8.3% were spontaneous preterm (RR, 3.8; 95% CI, 2.0-7.5).3 Additionally, although cesarean section and induced delivery were more common among this patient population, breast cancer was not associated with higher risks for maternal pregnancy complications. Furthermore, no pregnant women with breast cancer experienced gestational diabetes, pre-eclampsia, or stillbirth.

In this study, women diagnosed with cancer during pregnancy were identified in the Swedish Cancer and Medical Birth Registers between 1973 and 2017. Births with maternal breast cancer were matched with 10 births from cancer-free women by age, calendar year, and birth order.

Findings from a different study published in 

 show that although no significant differences in estrogen receptor (ER)–negative status were found in patients diagnosed with breast cancer during the first trimester (42%) and comparators (32%), second trimester diagnoses were associated with higher ER-negative status (62%).

 Furthermore, tumors in patients with diagnoses in the third trimester were larger, had more distant metastases, and were more often ER-negative vs comparators (54% vs 32%); they were also more likely to be luminal HER2 (22% vs 18%) or HER2-positive (22% vs 9%).

Additionally, mortality rates were higher for pregnancy-associated breast cancer than matched comparators. Disaggregated by trimester, the first trimester mortality rate was like that of matched comparators; 18.6 per 1000 person-years (95% CI, 6.0-57.8) vs 19.1 per 1000 (95% CI, 18.4-19.9). However, second and third trimester diagnoses were associated with significantly higher mortality rates; 42.0 (95% CI, 26.5-66.7) and 37.1 (95% CI, 24.9-55.3) per 1000, respectively.

In this study, the Swedish Cancer Register was used to identify women ages 18 to 44 diagnosed with invasive breast cancer from 1992 to 2018. Women with breast cancer diagnosed during pregnancy or with a postpartum diagnosis were matched 1:2 by year and age to comparators diagnosed with breast cancer not associated with pregnancy.

1. Increasing incidence of cancer during pregnancy, yet maternal and perinatal risks are low. News release. Karolinska Institutet. Published August 22, 2024. Accessed October 23, 2024. https://tinyurl.com/55chhb4f

23. Lundberg FE, Stensheim H, Ullenhag GJ, et al. Risk factors for the increasing incidence of pregnancy‐associated cancer in Sweden – a population‐based study. 

2024;103(4):669-683. doi:10.1111/aogs.14677

3. Lundberg FE, Gkekos L, Rosriguez-Wallberg KA, Fredriksson I, Johansson ALV. Risk of obstetric and perinatal complications in women presenting with breast cancer during pregnancy and the first year postpartum in Sweden 1973–2017: a population‐based matched study. 

2024;103(4):684-694. doi:10.1111/aogs.14555

4. Gkekos L, FE Lundberg, Humphreys K, Fredriksson I, Johansson ALV. Worse histopathology and prognosis in women with breast cancer diagnosed during the second trimester of pregnancy. 

 2024;9(4):102972. doi:10.1016/j.esmoop.2024.102972

While pregnancy-associated cancer risks increased with age, breast cancer during pregnancy tended to not impact obstetric risk. 

Breast Cancer May Not Affect Pregnancy Outcomes 

Up to 75% of women being treated for breast cancer report that they have experienced sexual dysfunction; however, there is a lack of patient-provider communication about these issues.

, Michelle Taylor, ANP, discusses the importance of having these discussions about sexual health, and remedies that oncology nurses and advanced practice providers can recommend for patients experiencing these effects.

“The shift comes when you just try [to have these discussions]. Then next time you have the conversation, it’s a little easier,” Taylor, a nurse practitioner for adult patients at Dignity Health Cancer Institute at St. Joseph’s in Phoenix, AZ, said. “Sometimes even if you don’t know what advice to give to that woman, just being heard is something that is often very important.”

: Why is sexual health important in women with breast cancer?

 When you're a breast oncology-specific [health care provider], you have a large population, typically, of women, between the age of 40 and 60, and they're working, they're in relationships. It's just not something that's talked about enough.

I think vaginal health specifically should be talked about more, because whether someone is engaging in intercourse or not, we know that vaginal dryness can be tied to things like more frequent [urinary tract infections], more frequency of urination, and incontinence. These can be pretty debilitating side effects. No, it's not a grade 3 diarrhea that's requiring emergent intervention, but it is a major quality-of-life issue.

Is there a specific type of cancer treatment that affects vaginal and sexual health?

The truth of the matter is, depending on which literature you're looking at, nearly 85% of men and women can experience sexual side effects from any modality of treatment for cancer therapy, including traditional IV chemotherapy, certainly these oral medications and even things like radiation and surgical intervention.

Sexual dysfunction occurs mainly in the breast cancer setting, as we are lowering estrogen levels, even when it's not a direct medication that does this, such as [goserelin acetate [Zoladex]) injections or an aromatase inhibitor. There is ovarian suppression that comes from chemotherapy, for example.

What are common sexual adverse effects from breast cancer treatment, and are there ways to treat them?

So, the first mechanism is typically vaginal dryness, and that can be layering on top of an already existing vaginal dryness. And then [there are] physical effects of stenosis of the vaginal canal, making intercourse uncomfortable, and also just simply the reduction in libido. There’s body dysmorphia that can happen to a woman who has gone through breast surgery, radiation, chemotherapy, so the physical changes that can happen as well.

So there's many layers to sexual health in this setting. And I think that there are ways to help curb some of this. A lot of the women are coming in with those existing symptoms already, and then we're exacerbating them.

Teaching a woman up front, being comfortable yourself, having those uncomfortable conversations once you let a woman know that you're here and willing to talk about really anything that they're experiencing [is important], I think they become more comfortable sharing those things. We tend to recommend proactive moisturization with things as simple as coconut oil, which is very safe for external moisturization, as well as lubrication for intercourse, but there are also products that contain hyaluronic acid that are vaginal moisturization products that are very easy to use overnight.

I can go on and on about this. It's a personal passion of mine, based on what we see our women experience here, but it is something that all oncology nurses should be aware of, no matter what setting they're working in.

A nurse practitioner discusses how breast cancer treatment can impact sexual health, and how nurses and APPs can guide patients through these effects. 

Pancreatic Cancer Action Network

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